Figure 164.1 Classic erythema migrans lesion.
Figure 164.2. Erythema migrans lesion.
Early disseminated
In some patients the spirochete disseminates hematogenously to multiple sites causing characteristic clinical features. Secondary annular lesions, sites of metastatic foci of Borrelia in the skin, develop within days of onset of EM in about half of US patients. They are similar in appearance to EM, but are generally smaller, migrate less, and lack indurated centers. In addition to musculoskeletal flu-like symptoms, mild hepatitis, splenomegaly, sore throat, nonproductive cough, testicular swelling, conjunctivitis, and regional and generalized lymphadenopathy may sometimes occur during early stages.
Diagnosis of early localized and early disseminated Lyme disease is based on clinical presentation, because serologic confirmation is often lacking and culture is not readily available. EM is diagnostic of Lyme disease although atypical lesions and rashes mimicking EM may be confusing. A history of a tick bite and residence or travel in an endemic area should be sought in patients presenting with rashes compatible with EM or a flu-like illness in summer. Specific immunoglobulin (Ig)M antibody responses against B. burgdorferi develop 2 to 6 weeks after the onset of EM. Immunoglobulin (Ig)G antibody levels appear approximately 6 weeks after disease onset but may not peak until months or even years into the illness. The highest titers occur during arthritis. Antibodies are typically detected using indirect immunofluorescence, enzyme-linked immunosorbant assay (ELISA), and immunoblotting (Western blot). Antibody responses may persist for months to years after successful eradication of infection. Two-tier testing is recommended, with ELISA screening done first and if positive an immunoblot performed.
Late disease
Late manifestations of Lyme disease typically occur months to years after the initial infection. In the United States, arthritis is the dominant feature of late Lyme disease, reported in approximately 60% of untreated individuals. Less often, individuals develop late chronic neurologic disease. Another late finding (years) associated with this infection is a chronic skin lesion, acrodermatitis chronica atrophicans, well known in Europe but rare in the United States. These late manifestations are discussed below.
Therapy
Early Lyme disease
The symptoms of early Lyme disease resolve spontaneously in most cases; therefore, the goals of therapy for early localized and mild early disseminated Lyme disease are to shorten the duration of symptoms and reduce the risk of developing serious late manifestations of infection. Treatment of these stages with oral antibiotics is adequate in the majority of patients (see Table 164.1). In patients with acute disseminated Lyme disease but without meningitis, oral doxycycline appears to be equally effective as parenteral ceftriaxone in preventing the late manifestations of disease. Initial studies of treatment for early Lyme disease reported therapy with phenoxymethyl penicillin, erythromycin, and tetracycline, in doses of 250 mg four times a day for 10 to 20 days, shortened the duration of symptoms of early Lyme disease. Phenoxymethyl penicillin and tetracycline were superior to erythromycin in preventing serious late manifestations of disease. Subsequent clinical trials have proven amoxicillin and doxycycline to be equally efficacious. Amoxicillin has largely replaced use of penicillin because of greater in vitro activity against B. burgdorferi. It is the preferred antibiotic choice in children under the age of 8 years. Concomitant use of probenecid has not been definitively shown to improve clinical outcome and is associated with a higher incidence of side effects. Doxycycline is usually selected over tetracycline because of its twice-daily dose schedule, increased gastrointestinal absorption and tolerability, and greater central nervous system (CNS) penetration. Doxycycline is effective in treating Anaplasma phagocytophilum (formerly known as Ehrlichia phagocytophila), an organism also transmitted by I. scapularis ticks; amoxicillin is not. Cefuroxime axetil, an oral second-generation cephalosporin, has been shown to be about as effective as amoxicillin and doxycycline in treating early Lyme disease; azithromycin, an azilide analog of erythromycin, somewhat less so. Macrolide antibiotics are not recommended as first-line therapy for early Lyme disease. Long-term follow-up of patients treated during early stages of Lyme disease support the current dosing regimens. Patients who received a 14- to 21-day course of a recommended antibiotic rarely developed late manifestations of illness. Recent studies have indicated that a 10-day course of doxycycline is adequate therapy for EM. Jarisch–Herxheimer-like reactions, an increased discomfort in skin lesions and temperature elevation occurring within hours after the start of antibiotic treatment, have been encountered in 14% of patients treated for early Lyme disease. They typically occur within 2 to 4 hours of starting therapy, are more common in severe disease, and are presumably due to rapid killing of a large number of spirochetes.
| Antibiotic regimen | Comments |
|---|---|
| Erythema migrans | |
| Amoxicillin, 500 mg 3 times daily for 14–21 d | Pediatric dose is 25–50 mg/kg/d three times daily |
| Doxycycline (Vibramycin), 100 mg twice daily for 10–21 d | Also effective against Anaplasma phagocytophium; not recommended for children under 8 years of age, pregnant or lactating women |
| Cefuroxime axetil (Ceftin), 500 mg twice daily for 14–21 d | Pediatric dose 30 mg/kg/d twice daily |
| Azithromycin (Zithromax), 500 mg daily for 7–10 d | Not recommended as first-line therapy; less effective than other regimens |
| Early disseminated disease (without neurologic, cardiac, or joint involvement) | |
| Initial treatment is the same as for erythema migrans except duration of treatment may be extended to 21–28 d | |
| Neuroborreliosis | |
| Isolated seventh nerve palsy | |
| Initial treatment is the same as for erythema migrans except duration of treatment is 21–28 d. The need for cerebrospinal fluid examination remains controversial | |
| All other neurologic manifestations (including meningitis, radiculoneuritis, peripheral neuropathy, encephalomyelitis, chronic encephalopathy) | |
| Ceftriaxone (Rocephin), 2 g daily for 14–30 d | 30-d regimen associated with fewer relapses in patients with chronic encephalopathy |
| Penicillin G, 20 million units daily for 14–28 d | Pediatric dose 200 000–400 000 units/kg/d every 4 h |
| Cefotaxime sodium (Claforan), 2 g every 8 h | Pediatric dose 150–200 mg/kg/d in 3–4 divided doses for 14–28 d |
| Doxycycline, 100 mg twice daily (oral or intravenous) for 14–28 d | No published experience in the United States |
| Carditis | |
| Doxycycline, 100 mg orally twice daily for 21 d | For first degree heart block, PR interval <0.3 s |
| Amoxicillin, 500 mg three times daily for 21 d | For first degree heart block, PR interval <0.3 s |
| Ceftriaxone, 2 g daily for 14–21 d | Optimal duration of therapy is unknown |
| Penicillin G, 20 million units daily for 14–30 d | Optimal duration of therapy is unknown, given in divided doses every 4 h |
| Arthritis | |
| Amoxicillin 500 mg four times daily for 30–60 d | Oral regimens should be limited to patients without evidence of neurologic involvement. Oral treatment may be extended for 60 d if no response to 30-d course |
| Doxycycline 100 mg two times daily for 30–60 d | |
| Cefuroxime axetil, 500 mg twice daily for 30–60 d | For patients with doxycycline and penicillin allergy |
| Ceftriaxone, 2 g daily for 14–30 d | |
| Lyme disease in pregnancy | |
| Amoxicillin, 500 mg three times daily for 21 d | For early localized disease only |
