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Lyme disease
is a tick-transmitted infection caused by Borrelia
burgdorferi. Symptoms include an erythema migrans
rash, which may be followed weeks to months later by neurologic, cardiac,
or joint abnormalities. Diagnosis is primarily clinical, but acute
and convalescent antibody titers may be helpful. Treatment is with antibiotics
such as doxycycline or, for serious infections, ceftriaxone.
Epidemiology
and Pathophysiology
Lyme disease was recognized in 1975 because of close clustering of cases in Lyme, Connecticut and is now the most commonly reported tick-borne illness in the US. It has been reported in 49 states, but > 90% of cases occur from Massachusetts to Maryland, in Wisconsin and Minnesota, and in California and Oregon. Lyme disease also occurs in Europe, across the former Soviet Union, and in China and Japan. Onset is usually in the summer and early fall. Most patients are children and young adults living in heavily wooded areas.
Lyme disease is transmitted primarily by Ixodes scapularis, the deer tick. In the US, the white-footed mouse is the primary animal reservoir for Borrelia burgdorferi and the preferred host for nymphal and larval forms of the deer tick. Deer are hosts for adult ticks but do not carry Borrelia. Other mammals (eg, dogs) can be incidental hosts and can develop Lyme disease. In Europe, sheep host the organism but do not develop the disease.
B.
burgdorferi enters the skin at the site of the tick bite. After 3 to 32 days, the organisms migrate locally in the skin around the bite, spread in lymph to produce regional adenopathy, or disseminate in blood to organs or other skin sites. The relative paucity of organisms in involved tissue suggests that most manifestations are due to host immune response rather than to the destructive properties of the organism.
Symptoms and Signs
Lyme disease has 3 stages: early localized, early disseminated, and late. The early and late stages are usually separated by an asymptomatic interval.
Erythema migrans (EM), the hallmark and best clinical indicator of Lyme disease, is the 1st sign of the disease. It occurs in at least 75% of patients, beginning as a red macule or papule, usually on the proximal portion of an extremity or the trunk (especially the thigh, buttock, or axilla), between 3 and 32 days after a tick bite. The area expands, often with central clearing, to a diameter ≤ 50 cm. Soon after onset, nearly 1⁄2 of untreated patients develop multiple, usually smaller, lesions without indurated centers. Cultures of biopsy samples of these secondary lesions have been positive, indicating dissemination of infection. EM generally lasts a few weeks (average, 3 to 4 wk). Evanescent lesions may appear during resolution. Mucosal lesions do not occur.
Symptoms of early-disseminated disease begin days or weeks after the appearance of the primary lesion when the bacteria spread through the body. This musculoskeletal, flu-like syndrome, consisting of malaise, fatigue, chills, fever, headache, stiff neck, myalgias, and arthralgias, may last for weeks. Because symptoms are often nonspecific, the diagnosis is frequently missed; a high index of suspicion is required. Frank arthritis is rare at this stage. Less common are backache, nausea and vomiting, sore throat, lymphadenopathy, and splenomegaly. Symptoms are characteristically intermittent and changing, but malaise and fatigue may linger for weeks. Some patients develop symptoms of fibromyalgia. Resolved skin lesions may reappear faintly, sometimes before recurrent attacks of arthritis, in late-stage disease.
Neurologic abnormalities develop in about 15% of patients within weeks to months of EM (generally before arthritis occurs), commonly last months, and usually resolve completely. Most common are lymphocytic meningitis (CSF pleocytosis of about 100 cells/μL) or meningoencephalitis, cranial neuritis (especially Bell's palsy, which may be bilateral), and sensory or motor radiculoneuropathies, alone or in combination.
Myocardial abnormalities occur in about 8% of patients within weeks of EM. They include fluctuating degrees of atrioventricular block (1st-degree, Wenckebach, or 3rd-degree) and, rarely, myopericarditis with chest pain, reduced ejection fractions, and cardiomegaly.
In untreated Lyme disease, the late stage begins months to years after initial infection. Arthritis develops in about 60% of patients within several months (occasionally up to 2 yr) of disease onset (as defined by EM). Intermittent swelling and pain in a few large joints, especially the knees, typically recur for several years. Affected knees commonly are much more swollen than painful; they are often hot, but rarely red. Baker cysts may form and rupture. Malaise, fatigue, and low-grade fever may precede or accompany arthritis attacks. About 10% of patients develop chronic (unremittent for ≥ 6 mo) knee involvement. Other late findings (occurring years after onset) include an antibiotic-sensitive skin lesion (acrodermatitis chronica atrophicans) and chronic CNS abnormalities, either polyneuropathy or a subtle encephalopathy with mood, memory, and sleep disorders.
Diagnosis
Cultures of blood and relevant body fluids (eg, CSF, joint fluid) may be obtained—primarily to diagnose other pathogens. Acute and convalescent antibody titers may be helpful; positive enzyme-linked immunosorbent assay (ELISA) titers should be confirmed by Western blot. However, seroconversion may be late (eg, > 4 wk) or occasionally absent, and positive IgG titers may represent previous infection. PCR testing of CSF or synovial fluid is often positive when those sites are involved. Consequently, diagnosis depends on both test results and the presence of typical findings. A classic EM rash strongly suggests Lyme disease, particularly when supported by other elements (eg, recent tick bite, exposure to endemic area, typical systemic symptoms).
In the absence of rash, diagnosis is more difficult because of the protean and often subtle symptoms. Early-disseminated disease may mimic juvenile RA in children and reactive arthritis and atypical RA in adults. Important negative findings include usually absent morning stiffness, subcutaneous nodules, iridocyclitis, mucosal lesions, rheumatoid factor, and antinuclear antibodies. Lyme disease presenting with a musculoskeletal, flu-like syndrome in summer may resemble ehrlichiosis, a rickettsial infection transmitted by the same tick (see Rickettsiae and Related Organisms: Ehrlichiosis). The lack of leukopenia, thrombocytopenia, elevated transaminases, and inclusion bodies in neutrophils helps distinguish Lyme disease. Acute rheumatic fever is considered in the occasional patient with migratory polyarthralgias and either an increased PR interval or chorea (as a manifestation of meningoencephalitis). However, patients with Lyme disease rarely have heart murmurs or evidence of a preceding streptococcal infection.
Late-stage disease lacks axial involvement, which distinguishes it from spondyloarthropathies with peripheral joint involvement. Lyme disease may cause Bell's palsy, fibromyalgia, and chronic fatigue syndrome and can mimic lymphocytic meningitis, peripheral neuropathies, and similar CNS syndromes.
In areas where Lyme disease is endemic, many patients with arthralgias, chronic fatigue, difficulty concentrating, or other troublesome but nonspecific symptoms attribute these to late-stage Lyme disease. Without a history of EM rash or other symptoms of early-localized or early-disseminated Lyme disease, few of these patients actually have Lyme disease. In such patients, elevated IgG titers indicating past exposure, not persistent infection, often lead to long and fruitless courses of antibiotic therapy.
Treatment
(See also the Infectious Diseases Society of America's Practice
Guidelines for the Treatment of Lyme Disease.) Most features of Lyme disease respond to antibiotics, but treatment of early disease is most successful. In late-stage disease, antibiotics eradicate the bacteria, relieving the arthritis in most people. However, a few people have persistent arthritis even after all the bacteria are gone because of continued inflammation.
Table 1: Spirochetes: Guidelines for Antibiotic Treatment of Adult Lyme Disease* shows adult treatment regimens for various presentations of Lyme disease. Treatment in children is similar except that doxycycline is avoided in children < 8 yr and doses are adjusted based on weight (see Table 3: Bacteria and Antibacterial Drugs: Usual Doses of Commonly Prescribed Antibiotics ). Duration of treatment has not been established by controlled trials, and recommendations vary in the literature.
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Table 1
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Guidelines for Antibiotic
Treatment
of Adult Lyme Disease*
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Early Lyme disease†
Amoxicillin , 500 mg tid po for 10–21 days or 1 g po q 8 h (some advise adding probenecid 500 mg po tid; probenecid is not needed if 1 g po q 8 h is used)
Doxycycline , 100 mg po bid for 10–21 days
Cefuroxime axetil, 500 mg po bid for 10–21 days
Azithromycin , 500 mg po once/day for 7 days (less effective than other regimens)
Neurologic manifestations
Bell's palsy (no other neurologic abnormalities)
Meningitis (with or without radiculoneuropathy or encephalitis)‡
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Cardiac manifestations
Ceftriaxone , 2 g IV once/day for 14–28 days
Penicillin G , 20 million units IV once/day for 14–28 days
Doxycycline , 100 mg po bid for 21 days (for mild carditis with 1st-degree heart block, PR interval ≤ 30 sec, normal ventricular function)
Amoxicillin , 500 mg po tid or 1 g po q 8 h for 21 days (for mild carditis with 1st-degree heart block, PR interval ≤ 30 sec, normal ventricular function)
Arthritis
Amoxicillin , 500 mg po qid or 1 g po q 8 h and probenecid , 500 mg po qid for 30 days (if no neurologic involvement)
Doxycycline , 100 mg po bid for 30 days (if no neurologic involvement)
Ceftriaxone , 2 g IV once/day for 14–28 days
Penicillin G , 20 million units IV once/day for 14–28 days
Acrodermatitis chronica atrophicans
Amoxicillin , 1 g po tid for 30 days
Doxycycline , 100 mg po bid for 30 days
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*Pregnant women may receive amoxicillin 500 mg tid for 21 days. No treatment is necessary for pregnant women who are seropositive but asymptomatic.
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†Without neurologic, cardiac, or joint involvement. For early Lyme disease limited to a single erythema migrans lesion, 10 days is sufficient.
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‡Optimal duration of therapy has not been established. There are no controlled trials of therapy > 4 wk for any neurologic manifestation of Lyme disease.
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Adapted from Rahn DW, Malawista SE: “Treatment of Lyme disease (special article).” In 1994 Year Book of Medicine, edited by GL Mandell, RC Bone, MJ Cline, et al. St. Louis, Mosby–Year Book, 1994, pp. xxi–xxxvi.
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For symptomatic relief, NSAIDs may be used. Complete heart block may require a temporary pacemaker. Tense knee joints due to effusions require aspiration and crutches. Patients with arthritis of the knee that persists despite antibiotic therapy may respond to arthroscopic synovectomy.
Prevention
Precautions against tick bite (see Sidebar 1: Rickettsiae and Related Organisms: Tick Bite Prevention ) should be taken by people in endemic areas. Deer tick nymphs, which attack humans, are small and difficult to see. Once attached to the skin, they gorge on blood for days. Transmission of B. burgdorferi does not usually occur until the infected tick has been in place for > 36 h. Thus, searching for ticks after potential exposure and removing them can help prevent infection.
A single dose of doxycycline 200 mg po has been shown to reduce the likelihood of Lyme disease after deer tick bite, but many clinicians do not recommend this treatment or limit it to patients with obviously engorged ticks. Patients with known tick bite can easily be instructed to monitor the bite site and seek care if rash or other symptoms occur; the diagnostic dilemma of Lyme is most prominent when there is no history of tick bite.
A vaccine, which was only moderately effective, has been removed from the market.
Last full review/revision November 2005
Content last modified November 2005
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