REVIEW
Diagnosis and Treatment of Lyme Disease

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Lyme disease is the most common tick-borne disease in the United States. This review details the risk factors, clinical presentation, treatment, and prophylaxis for the disease. Information was obtained from a search of the PubMed and MEDLINE databases (keyword: Lyme disease) for articles published from August 31, 1997, through September 1, 2007. Approximately 20,000 cases of Lyme disease are reported annually. Residents of the coastal Northeast, northwest California, and the Great Lakes region are at highest risk. Children and those spending extended time outdoors in wooded areas are also at increased risk. The disease is transmitted to humans through the bite of the Ixodes tick (Ixodes scapularis and Ixodes pacificus). Typically, the tick must feed for at least 36 hours for transmission of the causative bacterium, Borrelia burgdorferi, to occur. Each of the 3 stages of the disease is associated with specific clinical features: early localized infection, with erythema migrans, fever, malaise, fatigue, headache, myalgias, and arthralgias; early disseminated infection (occurring days to weeks later), with neurologic, musculoskeletal, or cardiovascular symptoms and multiple erythema migrans lesions; and late disseminated infection, with intermittent swelling and pain of 1 or more joints (especially knees). Neurologic manifestations (neuropathy or encephalopathy) may occur. Diagnosis is usually made clinically. Treatment is accomplished with doxycycline or amoxicillin; cefuroxime axetil or erythromycin can be used as an alternative. Late or severe disease requires intravenous ceftriaxone or penicillin G. Single-dose doxycycline (200 mg orally) can be used as prophylaxis in selected patients. Preventive measures should be emphasized to patients to help reduce risk.

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EPIDEMIOLOGY AND RISK FACTORS

Lyme disease is the most common tick-borne disease in the United States.2, 3, 4, 5 It has been reported in all 50 states1 and is also found in Europe and Asia.6 Lyme disease is most commonly reported in New England and the mid-Atlantic states, upper north-central regions, and several counties in northwestern California. Variation in zoonotic factors, including the presence of the white-footed mouse and white-tailed deer, which are important hosts in the life cycle of the Ixodes tick, account

ETIOLOGY AND VECTOR LIFE CYCLE

The white-footed mouse is the primary animal reservoir for Lyme disease in the United States. Black-legged ticks (I scapularis, deer ticks) are responsible for transmitting Lyme disease bacteria (B burgdorferi) to humans in the New England and Great Lakes areas. In the West, B burgdorferi is transmitted to humans by the western blacklegged tick (Ixodes pacificus), although the incidence of the bacteria in these ticks is much lower.

The nymphal and larval forms of the Ixodes tick feed primarily

Early Localized Infection

Lyme disease presents in most cases with a characteristic lesion resembling a bull's-eye or target, known as erythema migrans. The rash appears as a homogeneous, erythematous, annular lesion that may exhibit partial central clearing late in the clinical course of the disease (Figure 4). In Europe, cases tend to have more prominent central clearing. According to CDC guidelines, the diameter of the lesion must be at least 5 cm (average size, 15 cm) to qualify as erythema migrans, but smaller

DIAGNOSIS

The diagnosis of Lyme disease is based on clinical features in a person who has traveled to or lives in an endemic area. In most cases, it is appropriate to treat patients who have early disease and a high pretest probability, on the basis of signs and symptoms, after a tick bite by the Ixodes species. As with other tick-borne diseases, only 50% to 70% of patients recall a tick bite,16 often because the deer tick nymphs are small and go unnoticed.

Common laboratory tests usually are not

TREATMENT

According to guidelines from the Infectious Diseases Society of America,2 recommended antibiotic treatment for Lyme disease includes doxycycline for nonpregnant patients aged 9 years and older (100 mg orally, twice daily) or amoxicillin for patients younger than 9 years (50 mg/kg per day orally), which are generally effective in early disease. Second-choice treatment for adults is amoxicillin (500 mg orally, 3 times daily). Cefuroxime axetil (500 mg orally, twice daily; or 30 mg/kg per day

ANTIBIOTIC PROPHYLAXIS

In many areas of the United States, tick bites are extremely common. B burgdorferi is endemic in New England, the mid-Atlantic states, Minnesota, and Wisconsin. In these areas, the risk of infection after a prolonged bite can be high (10%-25%).23, 24 Risk of infection is much lower in the southern and western United States. Furthermore, there is no risk of transmission of B burgdorferi from an unengorged tick because the spirochetes require up to 36 hours after a bite to migrate from the tick

LATE LYME DISEASE

Some manifestations of Lyme disease arise or persist even after a 2-week course of oral antibiotic therapy. For example, a few patients treated with oral agents have subsequently manifested neuroborreliosis, which may require intravenous therapy.29 Furthermore, up to 10% of patients have persistent or recurrent joint swelling after treatment.2 Although this swelling eventually resolves, it can last for several months after treatment. Patients whose joint swelling persists after a second 4-week

POST-LYME DISEASE SYNDROME

No accepted definition or diagnostic criteria exist for post-Lyme disease syndrome, also called chronic Lyme disease and posttreatment chronic Lyme disease. The term is applied to people with otherwise-unexplained subjective symptoms lasting more than 6 months after completion of antibiotic treatment. Symptoms include fatigue, myalgias, arthralgias (without arthritis), and mood and memory disturbances (which can be shown through neuropsychological testing). Steere et al30 suggest that these

PREVENTION

Avoidance of tick bites is the most obvious means to prevent B burgdorferi infection. If people must be outside in areas where Ixodes ticks are found, they are advised to wear protective clothing and tick repellent containing N,N-diethyl-m-toluamide (DEET). Frequent skin inspection and prompt removal of ticks should also decrease the risk of infection. However, data regarding the efficacy of these measures are limited. Other measures, including burning or removal of vegetation in tick-harboring

CONCLUSION

Lyme disease is not uncommon and may affect people who spend time outdoors, especially in areas where Lyme disease is endemic. Affected people typically present with nonspecific symptoms and the characteristic erythema migrans rash; unfortunately, only 50% to 70% of patients recall a tick bite and thereby alert the physician to the diagnosis. Physicians should have a high index of suspicion for Lyme disease in areas known to harbor the disease. Prompt treatment with antibiotic therapy helps

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