American College of Physicians: Internal Medicine — Doctors for Adults ®

Advertisement

Experts spar over treatment for 'chronic' Lyme disease

From the January-February ACP Observer, copyright 2007 by the American College of Physicians.

By Deborah Gesensway

New clinical guidelines are fueling an old debate among infectious disease specialists over whether patients who experience persistent symptoms after being treated for Lyme disease benefit from staying on antibiotics.

An updated practice protocol from the Infectious Diseases Society of America (IDSA) argues against the existence of Borrelia burgdorferi chronically infecting most Lyme disease patients and disputes the practice of prescribing additional antibiotic regimens for patients with what they prefer to label "post-Lyme disease syndromes."

IDSA officials acknowledge that a small number of people suffer from persistent fatigue, joint aches and generalized pain for months after initial Lyme disease treatment, but they dispute the notion promoted by other physicians who treat Lyme disease and led by a small medical society, the International Lyme and Associated Diseases Society (ILADS), that long courses of antibiotics will help.


A female Black-Legged Tick (Ixodes scapularis), formerly known as the Deer Tick (Ixodes dammini).



"We don't know why problems develop after Lyme disease for a small minority of patients," said Paul G. Auwaerter, FACP, clinical director of the division of infectious diseases at Johns Hopkins University School of Medicine, who was a reviewer of the new guidelines. "Maybe it takes them a long time to clear the inflammatory responses, but we don't think that [the symptoms are] because of persistent infection."

Interpreting the evidence

According to the CDC, in 2005, 23,305 cases of Lyme disease were reported yielding a national average of 7.9 cases for every 100,000 persons. In the 10 states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons.

Recent studies have found that five to 15% of patients treated with antibiotics for Lyme disease report subjective symptoms six to 12 months after treatment, including fatigue, widespread musculoskeletal pain, cognitive problems or a substantial reduction in functional status.

However, the IDSA guidelines in the Nov. 1 issue of Clinical Infectious Diseases state emphatically that persistent symptoms do not usually translate into chronic infection. (The guidelines are online).

"There is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease," the guidelines state. "Antibiotic therapy has not proven to be useful and is not recommended for patients with chronic (six months or longer) subjective symptoms after recommended treatment regimens for Lyme disease."

IDSA's recommended treatment includes a single 10-28 day course of antibiotics followed occasionally by a second course.

The guideline also recommends treating some selected high-risk tick bites with a preventive single dose of doxycycline. To be eligible for this preventive treatment, the guideline says the tick should be reliably identified as a deer tick that was attached for 36 hours or longer (meaning engorged); that the patient was in an endemic area; and that the preventive treatment can be started within 72 hours of the time the tick was removed.

IDSA's updated guidelines were based on an evaluation of the evidence that exists from several published studies of antibiotic use for post-Lyme symptoms. According to Dr. Auwaerter, the largest and most rigorous one (a study by Klempner et al published in the New England Journal of Medicine in 2001) was stopped early because the group of patients treated with the antibiotics (parenteral ceftriaxone for one month followed by 60 days of doxycycline) were doing no better than those taking placebo pills. Whether taking antibiotics or placebo, in each group approximately one-third of patients improved, one-third stayed the same and one-third worsened.

A packed debate

The figurative debate between the groups became a literal one when Dr. and Auwaerter and Raphael B. Stricker, MD, medical director of Union Square Medical Associates in San Francisco and president of ILADS, addressed a packed house at a recent IDSA meeting.

ILADS members draw different conclusions from the same studies, Stricker told the audience. For instance, the Klempner study was an anomaly, he said. And other smaller, often unpublished studies have found a significant improvement in Lyme patients who were given IV ceftriaxone for 10 weeks or oral amoxicillin for three months compared with a placebo, he said.

In addition, he said, animal studies of mice, dogs and monkeys infected with the B. burgdorferi bacterium have identified spirochetes that survive treatment. In some patients, he said, "treatment may suppress but not eradicate B. burgdorferi."

Dr. Stricker presented studies suggesting that the patients treated for Lyme disease could still exhibit post-treatment infection through cultures of skin lesions, through PCR tests, from synovial fluid or in one case, from an iris biopsy.

He also presented as a basis for chronic Lyme disease 10 studies from published literature indicating treatment relapses and failures, six showing persistence despite treatment and four showing that treatment may suppress but not eradicate B. burgdorferi.

In addition to reviewing the data, they focused on several issues, including:

  • Do certain patients need longer courses of antibiotic treatment?
  • Are co-infections with other tick-borne diseases a factor when antibiotics fail?
  • Are some persistent symptoms caused by reinfection?
  • Are physicians diagnosing Lyme disease correctly?

False positives

Part of the quandary, explained Dr. Auwaerter, stems from the fact that many people diagnosed with Lyme disease don't actually have it. This can occur when physicians rely on tests that haven't been validated or approved by the FDA, such as the Lyme urine PCR, he said.

"When patients have only subjective complaints of fatigue and muscular-skeletal aches and a slip of paper that says they have Lyme disease from an unvalidated lab resource, it can make it very difficult to try to convince them that they might not have Lyme disease," he said. "Lyme is not unique for causing post-treatment fatigue, and post-infection fatigue is not necessarily a sign of persistent infection."

And physicians should understand that there can be false positive test results with standard Lyme serology especially in patients with only subjective complaints, he added.

General internists and family practitioners often order Lyme testing when there are neither physical symptoms, such as joint swelling, nor a history of possible deer tick bites in an endemic area. (Principally transmitted by the black-legged deer tick, the majority of the cases are concentrated in the Mid-Atlantic and northeast states. Other regions where there are significant numbers of cases include Wisconsin, Minnesota and northern California.)

As a result, patients end up seeing infectious diseases specialists for Lyme serology testing, he noted, which in misdiagnosed cases is "unnecessary, can have many false positives" and won't benefit from antibiotic treatment.

ILADS has published its own guidelines that allow for longer treatments, flexible antibiotic regimens and varied routes of administration (oral, intramuscular and intravenous) if the provider's clinical judgment warrants, Dr. Stricker said.

Dr. Stricker concluded his presentation at the IDSA meeting with some of the ILADS guidelines:

  • testing for Lyme disease and tick-borne coinfections by a laboratory proficient in this testing,
  • ruling out other diseases such as mercury toxicity, thyroid disease and B12 deficiency that can mimic neurologic Lyme disease,
  • performing brain scans or neuropsychiatric testing if neurologic symptoms are significant,
  • treating coinfections first, with success defined as a fourfold drop in serology (usually to undetectable levels),
  • using oral antibiotic therapy for predominantly musculoskeletal Lyme symptoms and parenteral antibiotics for predominantly neuropsychiatric Lyme symptoms, and
  • using rotating open-ended antibiotic regimens.

Dr. Auwaerter said rather than ordering subsequent courses of antibiotics for patients with persistent symptoms, he recommends graduated, low-impact exercise and conditioning to try to build up stamina. Other options include non-steroidal anti-inflammatory agents, antidepressants, stimulants, cognitive-behavioral therapy, and psychiatric consultations. But no studies have been done studying the efficacy of these other treatment options, only of longer-term antibiotic therapy, he added.

It is also key to rule out all other possible explanations. "At this point, post-Lyme syndrome is a diagnosis of exclusion, just like chronic fatigue or fibromyalgia," he said. "You have to be certain that there is not another explanation for their problems."

Deborah Gesensway is a freelance health care writer in Toronto.

Top

[PDF] Acrobat PDF format. Download Acrobat Reader software for free from Adobe. Problems with PDFs?

This is a printer-friendly version of this page

Print this page  |  Close the preview

Share

 
 

Internist Archives Quick Links

Have questions about the new ABIM MOC Program?

Have questions about the new ABIM MOC Program?

ACP explains the ABIM requirements and offers many free solutions to earn MOC points.

One Click to Confidence - Free to members

One Click to Confidence - Free to members ACP Smart Medicine is a new, online clinical decision support tool specifically for internal medicine. Get rapid point-of-care access to evidence-based clinical recommendations and guidelines. Plus, users can easily earn CME credit. Learn more