Lyme disease: 'Tis the season

New recommendations run the gamut from prophylaxis to post-Lyme syndrome.

Lyme disease, the most common tickborne infection in the United States, typically involves only the skin but may also affect the joints, nervous system, and heart. In its recent update of clinical practice guidelines first published in 2000, the Infectious Diseases Society of America confirms and strengthens earlier recommendations for antibiotic treatment, adds a section on prophylaxis, and addresses in more detail the question of post-Lyme syndrome.

“Because the majority of early cases present with erythema migrans, that's what most primary-care physicians will confront,” says Johan Bakken, MD, an infectious diseases specialist at St. Luke's Hospital, in Duluth, Minn., and a member of the panel that wrote the Guidelines.

Lyme disease prevention

Patients can most effectively prevent the disease by avoiding or reducing exposure to its vector, the deer tick (Ixodes scapularis and Ixodes pacificus); patients in areas where Lyme disease is endemic should be cautioned to wear protective clothing, use tick repellent when exposure is likely, and check the entire body for ticks daily.

When a tick bite does occur, the Guidelines do not recommend routine antibiotic prophylaxis or serologic testing. Instead, they suggest administering a single 200-mg dose of doxycycline to adults in whom it is not contraindicated, under specific circumstances in which transmission poses significant risk, defined as the presence of all three of the following:

• The tick can be identified as I. scapularis and has been attached for 36 hours or more, as estimated from the degree of engorgement or time of exposure.
• The tick was removed no more than 72 hours previously.
• Twenty percent or more of ticks in the locality are infected with Borrelia burgdorferi, the Lyme disease pathogen. Such areas include parts of New England, the mid-Atlantic states, Minnesota, and Wisconsin.

To prescribe antibiotic prophylaxis appropriately, the authors recommend that clinicians in high-prevalence areas familiarize themselves with I. scapularis in its nymphal and adult forms at various levels of engorgement. The Guidelines include illustrations to facilitate identification.

“Prophylaxis is more an option than an absolute,” Dr. Bakken says, noting that the recommendation is based on a single study and that Lyme disease, if diagnosed promptly when the rash appears (generally 7-14 days after a bite), is almost always easy to treat. “Once the tick bite is recognized, there's the opportunity to keep it under observation (for up to one month) and watch for erythema migrans,” he states.

Treatment of early Lyme disease The majority of early infections are manifested by a single erythema migrans lesion, an expanding round or oval patch ≥5 cm at the site of the tick bite. Secondary lesions, similar but smaller, represent dissemination of the infection. (A small lesion that appears within 48 hours at the site and does not grow is probably a hypersensitivity reaction.) Recommendations for antibiotic treatment (see table) are essentially unchanged from the 2000 document but have been refined and “solidified” by subsequent data, notes Dr. Bakken.

Drugs of choice when Lyme manifestations are confined to the skin are oral doxycycline (100 mg b.i.d.), amoxicillin (500 mg t.i.d.), or cefuroxime axetil (500 mg b.i.d.) for 14 days. All three agents have demonstrated efficacy for erythema migrans; doxycycline is also effective against human granulocytic anaplasmosis, another Ixodes-borne disease.

The Guidelines recommend macrolide antibiotics only for patients who are intolerant of or should not use any of the first-line drugs. “There is a step-down in success rate with these agents, which was confirmed by recent studies,” Dr. Bakken observes. Other antibiotics (first-generation cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole, et al) are not recommended.

Extracutaneous manifestations of Lyme disease during this early period, which have been reported less commonly in recent years than before, include neurologic and cardiac involvement. Recommended treatment for meningitis or radiculopathy associated with early Lyme disease is parenteral antibiotics: IV ceftriaxone 2 g/day for 14 days is the drug of choice, but cefotaxime or penicillin G can be used as alternatives. There is some evidence that oral doxycycline 200-400 mg/day can be effective for patients unable to use beta-lactam antibiotics.

The Guidelines recommend the standard regimen for erythema migrans be given to patients who have seventh cranial-nerve palsy without central nervous system involvement. When cerebrospinal fluid findings are suggestive or patients exhibit such symptoms as severe headache or nuchal rigidity, the previously recommended meningitis regimen is indicated.

Cardiac manifestations of early Lyme disease are atrioventricular heart block or myopericarditis. The Guidelines suggest either oral or parenteral antibiotic therapy for these patients. However, hospitalization and IV antibiotics are likely to be necessary, at least initially, particularly in the presence of such symptoms as dyspnea or chest pain.

Late Lyme disease

Lyme arthritis, which is usually associated with untreated or inadequately treated early Lyme disease, has been reported in no more than 10% of patients in recent case series. The same oral antibiotics recommended for erythema migrans are indicated in this situation but for a longer period (28 days). If joint swelling persists or recurs, the Guidelines recommend a second course of the same regimen or two to four weeks of IV ceftriaxone.

Late neurologic disease requires the regimen recommended for early Lyme disease meningitis or radiculopathy for up to four weeks. Response, the Guidelines say, “is usually slow and may be incomplete.”

Post-Lyme disease

The persistence of diverse symptoms for weeks, months, or even years after adequate treatment — variously termed “chronic Lyme disease,” “post-treatment chronic Lyme disease,” and “post-Lyme disease syndrome”— has been the subject of confusion and controversy. The most recent Guidelines devote a fuller discussion to the issue than the 2000 version.

Neurologic or arthritic manifestations may linger in some patients, the authors suggest, because of delay in resolution of inflammation associated with Lyme disease beyond the period of infection itself; some sequelae, such as weakness of facial muscles, may reflect irreversible neurologic damage.

Nonspecific or subjective symptoms, such as fatigue, cognitive difficulties, and widespread musculoskeletal pain, have also been reported, but whether they are actually more common than in non-Lyme-infected individuals is unclear.

There is little evidence to suggest that B. burgdorferi infection persists after adequate initial therapy. In view of the fact that the utility of extended antibiotics for chronic symptoms is unproven while their risks are well documented, the authors do not recommend them in this context.

Patients' suffering should not be discounted, Dr. Bakken emphasizes. “They need to be told about the lack of evidence for prolonged antibiotic treatment, and their complaints should be treated symptomatically.”

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America was published in Clinical Infectious Diseases (2006;43:1089-1134). The Guidelines are available online at: www.journals.uchicago.edu. Accessed February 15, 2008.

Mr. Sherman is a medical writer in New York City.