INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
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Background

Lyme disease is a systemic infection caused by the spirochete Borrelia burgdorferi. The bacterium is inoculated into the skin by a tick bite. The tick is almost always of the genus Ixodes.

Although various parts of the syndrome were described in Europe more than 100 years ago, the full spectrum had not begun to be identified until 1975, when a cluster of statistically improbable cases of juvenile arthritis occurred in Connecticut. This outbreak stimulated intensive clinical and epidemiologic research that led to the discovery of the causative agent, the ecology, an expanding list of clinical manifestations, and the geographic range. Furthermore, the initial antibiotic responsiveness of the cutaneous manifestations described in the European literature was confirmed and extended.

Pathophysiology

The pathophysiology of Lyme disease is incompletely understood. While active infection by the spirochete causes many manifestations, others may be caused by immunopathogenic mechanisms. Although any body part can be involved, the organism shows a distinct tropism for the skin, CNS, heart, joints, and eyes.

The bacterium is introduced into the skin with a bite from an infected Ixodes tick. In the northeastern and upper midwestern United States, Ixodes scapularis is the vector. In other parts of the country and world, other Ixodes species serve that function. Other ticks (eg, Amblyomma americanum) and insects can carry B burgdorferi, but Ixodes tick bites are thought to cause the vast majority of cases. In the southern and mid-central United States, a Lymelike illness has been reported; the vector appears to be A americanum, and the causative organism or organisms is likely to be a related spirochete. One such organism, named Borrelia lonestarii, has been cultured in a single case.

Once in the skin, the spirochete can (1) be overwhelmed and eliminated by host defense mechanisms; (2) remain viable and localized in the skin where it produces the pathognomonic skin lesion, or erythema migrans (EM); or (3) disseminate through the lymphatics or blood. Hematogenous dissemination can occur within days to weeks of initial infection; the organism can travel to the skin, heart, joints, CNS, and other parts of the body.

Study findings show that in roughly 10% of patients with isolated EM and no systemic symptoms, B burgdorferi can be cultured or that its DNA can be detected in the bloodstream. Using high volume (9 mL) of plasm for culture, one 2005 study suggests that nearly 44% of patients are spirochetemic, some of them with a single skin lesion and no systemic symptoms.¹ Also, early in the course of the disease when EM is still present, the spirochete and its DNA have been isolated from the cerebrospinal fluid (CSF), indicating early CNS penetration. This penetration can occur even in the absence of neurologic symptoms.

The organism can also persist in skin (and possibly in the CNS) for years without causing symptoms. Experimentally, the spirochete can penetrate human fibroblasts and live intracellularly, even when the extracellular medium contains ceftriaxone well above bacteriocidal levels for the spirochete. Clinically, organisms have been cultured from skin many years after primary infection. This mechanism may allow the spirochete to elude the normal host defense mechanisms directed against it.

As with syphilis, the disease classically is divided into stages: early localized, early disseminated, and late. However, distinct cutoff points between the stages are frequently unclear. Early localized Lyme disease refers to isolated EM and patients with an undifferentiated febrile illness. Early disseminated disease refers to the extracutaneous manifestations and secondary skin lesions that occur during the first weeks to months after infection. Late Lyme disease refers to later manifestations (usually in the nervous system and joints) that occur months to years later. Many patients initially have EM; however, in others, neurologic or rheumatologic complaints may be the initial symptoms, either because EM is not present or because it was unrecognized or misdiagnosed.

Frequency

United States

The Centers for Disease Control and Prevention (CDC) track cases of Lyme disease by using strict surveillance criteria (not designed for diagnosis of individual cases). The incidence has been increasing over time. This is not simply a result of increased recognition, since in states that perform active surveillance, true incidence and geographic range have increased. The likely causes of this increase are expansion of deer herds and the expanded range of the vector.

In 2001, the CDC reported 17,029 cases and, in 2002, that number rose to 23,763—a 40% increase. Year-to-year variation can be significant. More than 95% of cases come from 12 states (Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin). Even within these states, incidence can be quite variable from county to county and even neighborhood to neighborhood.

Overall in the United States, incidence is 6.0-8.2 cases per 100,000 population (2001 and 2002 data). However, in Connecticut in 2001, the rate was nearly 134 cases per 100,000 population, and, on the island of Nantucket, Massachusetts, the rate exceeded 1000 cases per 100,000 population.

Epidemiologic data suggest that the actual incidence of Lyme disease could be as much as 10 times higher than the CDC data indicate. This probably is a result of a restrictive case definition from the CDC, inevitable misdiagnosis, and the fact that physicians tend to underreport reportable diseases of all kinds.

International

Lyme disease exists throughout the world, including Scandinavia; central, southern, and western Europe; the former Soviet Union; Japan; and China. While Lyme disease is far more common in the northern hemisphere, occasional cases have been reported in more tropical locales, and it may exist in Australia. Ecology for the disease differs in various parts of the world. Furthermore, different strains of the organism are present in Europe and very likely account for differences in clinical manifestations; these have implications for diagnostic testing and vaccination strategies.

Mortality/Morbidity

Rare fatalities are reported in patients with Lyme disease.

• Some fatal cases occur in patients who were simultaneously co-infected with other tick-borne pathogens. In North America, these other infections are generally babesiosis and ehrlichiosis. In Europe, in addition to these 2 organisms, fatalities have been reported with co-infecting tick-borne encephalitis, a tick-borne flavivirus.
• Patients with neurologic disease that is not promptly diagnosed and treated can have neurologic damage that can be difficult to treat. These fixed neurologic deficits may not respond to antibiotics.
• Similarly, some genetically predisposed patients with arthritis may have ongoing joint inflammation that does not respond to further antibiotic therapy.

Race

No known differential frequency exists in patients of different races; however, EM maybe more difficult to diagnose in dark-skinned individuals.

Sex

Developing Lyme disease is more a function of tick exposure than sex. Likely for this reason, the disease is slightly more common in males than in females.

Age

Lyme disease occurs in patients of all ages. However, a bimodal peak exists: one at age 5-14 years and a second one at 50-59 years.

• About 25% of cases occur in children younger than 14 years.
• The likelihood of contracting Lyme disease is related more to tick exposure than to age, sex, or race per se.

CLINICAL

Section 3 of 11  

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• Differentials
• Workup
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History

Because only about 25-30% of patients with Lyme disease recall the bite, history taking must be directed toward determining the epidemiologic probability of a tick bite. Because Lyme disease can affect many body parts, many presenting complaints can exist. Examples may include the following:

• Systemic manifestations
• • Fever is generally low grade. A high-grade fever or toxic appearance suggests co-infection, such as ehrlichiosis or babesiosis, or an alternative diagnosis.
  • Fatigue is common.
  • Myalgias and arthralgias occur early. Frank arthritis (ie, joint swelling, redness, pain) usually is a later manifestation but can occur in the early disseminated phase.
  • Flulike illness (undifferentiated febrile illness) may occur. Although the frequency of this is unknown, the phenomenon of Lyme disease with typical flulike symptoms of fevers, chills, myalgias, arthralgias, and malaise (without rash) is well documented. The season of onset, epidemiologic likelihood of a tick bite, paucity of respiratory and GI symptoms, and prompt response to antiborrelial therapy are diagnostic clues.
• Cutaneous symptoms
• • The classic rash, erythema migrans (EM), is present in about 75% of patients. Because it is neither pruritic nor painful (although it can be either), some patients may have the rash but not notice it. EM can occur in the same patient more than once.
  • About 20% of patients with Lyme disease have multiple lesions (from hematogenous dissemination). The higher figure is from earlier studies; current information suggests that the rate of multiple lesions is closer to 20%.
  • Borrelial lymphocytoma, a nodule usually found on the ear lobe or areola of the nipple, develops in some patients early in the course of disease. This is more common in Europe.
  • Almost exclusively observed in Europe, acrodermatitis chronicum atrophicans is a rash that patients describe as inflammation or thinning of the skin, usually on the distal legs and hands.
• Neurologic symptoms
• • Headache can occur in early infection as a nonspecific finding and can herald CNS penetration and lymphocytic meningitis. The headache of Lyme disease typically is described as waxing and waning, and the severity varies from mild to severe, even in patients with frank meningitis.
  • Patients notice facial weakness, which is similar to a typical Bell palsy and which can be the presenting symptom of Lyme disease. About 25% of patients with borrelial facial palsy have bilateral involvement, which may be sequential and is a point of differential diagnostic significance. Other than Lyme disease and Guillain-Barré syndrome, bilateral seventh nerve palsy is rare.
  • Radicular pain can occur and present as acute disk disease. More common in European patients, radicular pain may be associated with lymphocytic pleocytosis (Bannwarth syndrome).
  • Late Lyme disease can cause paresthesias or pain due to peripheral neuropathy and personality, cognitive, and sleep disturbances from chronic encephalopathy. All sorts of neurologic syndromes caused by Lyme disease involving nearly every part of the CNS and peripheral nervous system have been reported in numerous case reports; therefore, Lyme disease may produce numerous symptoms. Although the likelihood that these other symptoms result from Lyme disease in any particular patient may be small, the clinician must remain open minded to this possibility.
• Cardiovascular involvement
• • Cardiovascular involvement occurs in fewer than 10% of patients with untreated Lyme disease and is more common in male patients than in female patients.
  • Palpitations, lightheadedness, and syncope may be a manifestation of varying degrees of heart block, including complete heart block, which occurs in 50% of patients with cardiac involvement. Lyme disease is an important reversible cause of heart block.
  • Chest pain and dyspnea can occur in the setting of Lyme pericarditis, myocarditis, and myopericarditis. Tamponade has been reported.
• Migratory pains in and around the joints and muscles
• • Migratory pain may occur from myositis, tendonitis, and bursitis.
  • These symptoms classically wax and wane over hours or days.
  • Later, arthritis occurs generally with swelling, redness, and pain in one or a few large joints, typically the knees.
  • Synovitis occasionally occurs in the early-disseminated phase of Lyme disease.
• Red, itchy eyes from conjunctivitis
• • Red, itchy eyes are the most common ocular symptom.
  • Blurred vision and eye pain can occur from keratitis and iritis. Unilateral blindness from panophthalmitis has been reported as well.
• Nausea and vomiting

Physical

The physical examination in patients with Lyme disease can reveal numerous findings, depending on the target organs involved and the phase of the disease at presentation. In addition to fever, findings may include the following:

• Dermatologic findings
• • Classic EM is an erythematous papule or macule that occurs at the site of the tick bite (1-33 d later; average, 7-10 d). Often, a central punctum is found at the site. The size varies enormously (as large as 70 cm; average, 16 cm) and depends on disease duration. Central clearing, a phenomenon emphasized in earlier literature, occurs in only a minority of cases in North America (about 40% in one study of culture-proven EM).² Central clearing is more common in European patients than in North American patients.
  • Although lesions are defined, for surveillance purposes, as being greater than 5 cm in size, smaller lesions that are culture positive for B burgdorferi have been reported. EM may not be pathognomonic for Lyme disease; similar lesions are found in patients with a similar tick-borne disease found across the southern United States. In this disease, called southern tick-associated rash illness (STARI), or Master disease, a similar rash is seen. While differences exist between the two rashes as a group, significant overlap exists in individual cases.
  • EM usually is flat, round, or oval and monocyclic. Generally, neither itching nor pain is present. The rash enlarges a few centimeters per day and fades, even if untreated, after a few weeks. The rash can be triangular or linear and is sometimes fleeting in duration. Rash location is another important diagnostic clue.
  • The clinician must be able to recognize atypical manifestations of EM, such as necrotic and vesicular lesions. The lesion may have central darkening or be uniform in color, and the edges may be raised. Scaling is unusual.
  • EM rarely is found on the hands and feet (unlike spider and other arthropod bites). Ticks tend to bite where natural barriers impede their forward motion (eg, axillary or gluteal folds, hairline, areas near elastic bands in bra straps or underwear). In children, the scalp, face, and hairline are more common locations.
  • Approximately 20% of patients with EM have secondary lesions. These lesions generally are smaller than the primary one, lack the central punctum, and are not necrotic or vesicular.
  • Borrelial lymphocytoma most frequently is observed in European patients. This finding can be early or late and can follow or occur concurrently with EM. It is a reddish purple nodule on the ear lobe or the nipple (other locations are possible).
  • Acrodermatitis chronicum atrophicans is nearly exclusively observed in European patients. The two phases are an inflammatory phase with edema and erythema in the distal extremities and a scarring phase with atrophy and skin as thin as cigarette paper. B burgdorferi has been cultured from lesions in which the primary infection occurred over 10 years prior.
• Neurologic signs
• • Neck stiffness can occur early, with or without frank meningitis.
  • Facial nerve palsy is a lower motor neuron lesion that causes facial weakness of both the lower face and forehead. It can be bilateral. As in idiopathic Bell palsy, sometimes a polycranial neuropathy exists with any nerve involved; this more commonly is reported in the European literature. Nearly every cranial nerve has been reported to be involved, although this is uncommon.
  • Weakness and abnormal sensation can occur because of meningoradiculitis and more commonly is reported in European patients. Diminished reflexes can occur with this syndrome. CSF frequently reflects pleocytosis.
  • Neuropsychiatric testing and mini-mental status testing may uncover cognitive, memory, and personality changes that occur in late Lyme encephalopathy.
  • Peripheral axonal neuropathy can lead to patchy, generally distal abnormalities in sensation. Sensory findings are more pronounced than motor findings.
• Cardiovascular findings
• • In patients with complete heart block, Canon A waves may be observed in the neck. A slow or irregular pulse may be palpated.
  • A cardiac rub, S₃ and/or S₄, may be auscultated in patients with myocarditis or pericarditis. Signs of tamponade very rarely can occur. In patients with chronic cardiac involvement with congestive heart failure, typical signs of congestive heart failure may be present.
• Musculoskeletal findings
• • Muscle tenderness can result from myositis; tenderness of tendons and periarticular structures may be present.
  • Frank arthritis can occur after weeks, months, or years and may lead to erythema, edema, synovial effusion, and tenderness of the affected joints. Usually, this is a monoarthritis or oligoarthritis involving large joints, especially the knee. Swelling often is disproportional to the tenderness.
• Ocular signs
• • Conjunctival erythema and injection or retinal hemorrhages and exudates may be present.
  • On slit lamp examination, signs of keratitis and cells in the anterior chamber from iritis may be seen.
  • In children (especially in North America), papilledema may be present in a pseudotumor cerebri–like syndrome.
• Other signs - Splenomegaly, hepatomegaly, regional lymphadenopathy

Causes

Lyme disease is caused by infection with the spirochete, B burgdorferi, the complete genome of which has been described recently.

• The species Borrelia burgdorferi sensu lato has several well-characterized groups that may lead to different clinical manifestations. These 3 groups are B burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. Other strains, which may be sufficiently different in their genetic structure to be considered separate strains, exist; however, most of these are nonpathogenic to humans. This is an area of active research.
• • B burgdorferi sensu stricto is present in most North American isolates.
  • B afzelii is common in Europe and is frequently isolated in patients with acrodermatitis chronicum atrophicans.
  • B garinii, more common in Europe, is commonly isolated in patients with lymphocytic meningoradiculitis (Bannwarth syndrome) and white matter encephalitis.
• Occupational or recreational activities that place an individual in contact with ticks are the major risk factors.
• Arthritis that is nonresponsive to antibiotics may develop in some genetically predisposed individuals (ie, those who have the HLA-DR4 antigen).
• Some patients will have persistent or recurrent symptoms after what is considered adequate antibiotic therapy for Lyme disease. This phenomenon has been termed chronic Lyme disease, or post-Lyme syndrome. The cause for this is controversial.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory testing depends entirely on the presenting problem of the patients. Evaluation of the CBC, erythrocyte sedimentation rate, and liver function generally is unnecessary, and serologic tests can be misleading if performed in the wrong setting.
• • The patient with solitary, typical EM requires no laboratory testing whatsoever. Expected results for the CBC and erythrocyte sedimentation rate are likely normal. At this stage of illness, serologic testing is unnecessary because the pretest probability of Lyme disease is high, and the sensitivity of the serologic test is low (during the first several weeks).
  • Leukopenia or thrombocytopenia suggests co-infection with Ehrlichia or Babesia species.
  • Elevation of at least one liver function test result is reported to occur in 40% of patients with Lyme disease. This finding also is common in ehrlichiosis.
• Culture of B burgdorferi
• • Because of the organism's fastidious growth requirements, culture has not been a useful test in the past; however, this situation is improving. Its usefulness depends on the specimen being cultured. Nevertheless, in routine practice, borrelial cultures are often unavailable.
  • In the skin, where findings are most likely to be positive, culturing is least likely to be clinically useful, except in cases of atypical rash.
  • In other body fluids (eg, blood, synovial fluid, CSF), the yield is lower. However, recent data suggest that if a high volume (9 mL) of plasma is used, approximately 44% of patients with EM are determined to be spirochetemic at presentation.

Imaging Studies

• Imaging studies are almost never indicated in patients with Lyme disease who present with early syndromes. Patients with some clinical syndromes may require imaging studies, depending on the specifics of the case. For example, a patient with fever and severe back pain, with signs of radiculopathy, might require spine imaging.

Other Tests

• Serologic testing for Lyme disease is complex. Rational ordering and interpretation of these test results requires some understanding of the basic underlying principles and performance characteristics of the test.
• Most importantly, the most commonly performed test measures antibodies to various proteins of the spirochete, some of which are very specific for the organism and others of which are nonspecific. The test results do not rule in or rule out Lyme disease; however, the results make a clinical diagnosis of Lyme disease more (or less) likely.
• The CDC recommends a 2-step procedure consisting of a screening enzyme-linked immunoassay (ELISA) (or immunofluorescent assay [IFA]) and a confirmatory Western blot for specimens that have positive or equivocal results with the ELISA. Furthermore, in patients with a high likelihood of having Lyme disease (eg, classic EM in an endemic area), no serologic test should be ordered. Conversely, in a patient with a low pretest likelihood of having Lyme disease (eg, someone with vague symptoms where the test is being used as a screening test), testing is also not recommended because in such a population, the number of false-positive results greatly outnumbers the true positive results.
• Numerous conditions (eg, viral and bacterial infections, inflammatory diseases, neoplasms) can cause false-positive ELISA results. Also, a small percentage of the healthy population has positive test results with ELISA testing. For these reasons, confirmatory Western blot testing is recommended.
• Timing is extremely important. Seroconversion may take several weeks in patients infected with the spirochete, so early seronegativity is to be expected.
• Even occasional patients with facial nerve palsy or carditis (ie, early disseminated disease) may be seronegative on presentation. However, testing is recommended in these individuals. Furthermore, early or partial treatment with antibiotics may blunt or abrogate the subsequent serologic response. Some patients with late disease are seronegative, but significant controversy exists regarding the frequency of late seronegativity. Most authorities suggest that this phenomenon is rare.
• On the other hand, patients with prior Lyme disease may have persistently positive results. Also, vaccinated patients will have a positive ELISA result (although Western blot results should be negative). Lack of attention to the details of the test result and the reliability of the laboratory performing the test might lead the physician to an erroneous conclusion about the cause for a given patient's symptoms.
• Patients may remain seropositive for long periods; therefore, serologic test results cannot be used as a proof or test of cure. Also, if a patient with past Lyme disease who remains seropositive comes in with new symptoms, care should be taken to not necessarily ascribe these new symptoms to Lyme disease.
• The emergency physician must remember 2 important concepts. First, a negative Lyme test result does not indicate the absence of disease, nor does a positive result indicate the presence of disease. Second, a positive result is not required for someone with clear-cut EM; these early-presenting patients frequently have negative results, and they should be treated for EM empirically.
• In the last few years, research on newer serologic tests—specifically the C6 peptide and the VslE—is promising. These test results may well turn positive earlier and revert to negative after successful treatment. As of mid 2005, these tests have not been incorporated into routine clinical practice and the CDC recommendations above still stand.

Procedures

• Because the spirochete can enter the CSF early in the course of infection and because the finding of meningitis (defined here as abnormal CSF in the setting of active Lyme disease) changes the treatment, many physicians have a low threshold for performing a lumbar puncture in patients with EM and any CNS symptoms or in patients with isolated seventh nerve palsy due to Lyme disease. The finding of elevated protein levels or pleocytosis mandates parenteral therapy. Definitive data to either support or refute this practice are lacking.
• In addition, a lumbar puncture ought to be performed if Lyme meningitis is in the differential diagnosis.
• Occasional patients with Lyme disease–related heart block will require temporary cardiac pacing. The indications for cardiac pacing are the same as for any other patient with varying degrees of heart block. Permanent wires are very rarely needed.

TREATMENT

Section 6 of 11  

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• Follow-up
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Emergency Department Care

ED care of patients with Lyme disease depends on the presenting complaint. In general, Lyme disease is not fatal, and the emergency physician may be able to consult specialists and refer the patient to a primary care physician.

Treatments for tick bites, EM, early disseminated disease, and arthritis are as follows:

• Tick bite without other symptoms or signs: Several factors influence the decision to treat tick bites with therapy to prevent Lyme disease.
• • Animal studies have shown that transmission of infection is unlikely if the duration of tick attachment is less than 24 hours, and transmission is very likely for ticks attached for longer than 72 hours. This finding presumes that the tick is infected in the first place and the percentage of Ixodes ticks that are infected varies with geography. It also depends on the species of tick. Non-Ixodes ticks and other insects, although they can contain the organism, are highly unlikely to cause disease. The one clinically relevant exception may be bites by A americanum in the central and southern midwestern United States, but data exist on treating these tick bites prophylactically at the present time.
  • Several randomized placebo-controlled studies have been conducted to investigate prophylactic treatment of tick bites. All revealed that the rate of symptomatic infection and asymptomatic seroconversion is about 2% in placebo groups. This study occurred in areas in which about 15-30% of ticks were infected; this finding indicates that many bites from infected ticks do not result in transmission of the spirochete. These studies form the basis of the often-cited recommendation to withhold tick bite prophylaxis.
  • In 2001, a study was published showing that only female nymphal ticks transmitted Lyme disease.³ It also corroborated the finding that duration of attachment is an important marker for transmission.
  • However, findings of other studies of culture-proven EM in the United States and Europe suggest that a nontrivial minority of patients had tick attachments of less than 24 hours, some less than 6 hours. Therefore, one cannot be dogmatic with the criterion of duration of tick attachment. Poor technique in tick removal also may facilitate infection. For further information, see Tick-borne Diseases, Introduction.
  • Although most patients do not require treatment, consider tick bite prophylaxis on a case-by-case basis. Base the decision on the species of the tick, duration of attachment (degree of engorgement of the tick is a surrogate marker), geography (percentage of ticks infected where the bite took place), method of tick removal, anxiety level of patient, and pregnancy (lower threshold to treat pregnant women).
  • After performing this exercise in clinical decision-making, one may decide to treat a given patient with prophylactic antibiotics. In the studies mentioned previously, no patient in the treatment group (which received 10 d of antibiotic treatment) had the disease. Historically, if one were to choose to treat, 10 days of oral amoxicillin, doxycycline, or cefuroxime axetil would seem prudent, depending on patient factors such as age, allergy, and pregnancy.
  • In one of the most recent studies (2001), a single 200-mg dose of doxycycline was used for prophylaxis with excellent results.³
  • Serologic testing plays no role in the care of patients with tick bites.
• Solitary EM: Oral antibiotics (eg, amoxicillin, doxycycline, cefuroxime axetil, erythromycin, azithromycin, amoxicillin-clavulanate) should be administered for 10-30 days. The author recommends therapy of 3 weeks duration. Given recent findings that early disseminated Lyme disease responds very well with 21 days of oral therapy,⁴ not exceeding that duration for localized disease seems logical. That said, one recent study suggests that 10 days of antibiotic treatment is just as effective as 20 days.⁵
• Early disseminated disease findings such as isolated facial palsy or secondary skin lesions (not meningitis) or disease with first-degree heart block (not a high-degree heart block) may be treated with oral antibiotics for 21-30 days. Recent data show that 21 days of oral doxycycline is as effective as 14 days of intravenous ceftriaxone for disease in this stage.
• Early disseminated disease with meningitis or a high-degree heart block may be treated with intravenous ceftriaxone for 2-4 weeks. In the case of heart block, a permanent pacemaker rarely is necessary, but close monitoring in a telemetry unit is warranted. Once patients are no longer dependent on the pacemaker, their intravenous antibiotics may be switched to oral antibiotics. Occasionally, prednisone may hasten resolution of the conduction defect.
• Arthritis may be treated with oral antibiotics for 30-60 days, and intravenous ceftriaxone may be administered for coexistent neurologic disease.

Consultations

The need for consultation depends on the emergency physician's confidence in the clinical diagnosis.

• At times, input from a dermatologist, neurologist, infectious diseases specialist, or cardiologist assists in making a firm diagnosis, particularly in the setting of chronic disease.
• Always refer patients to primary care physicians to monitor for later manifestations of the disease.

MEDICATION

Section 7 of 11  

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• Introduction
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• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Early Lyme disease usually responds well to antibiotics. Data regarding the route and duration of therapy are evolving and are, to some extent, controversial. Nevertheless, several general principles apply.

Solitary EM can be treated for 10-30 days with oral regimens. Rashes of longer duration and more severe symptoms may require a longer duration of therapy. Because good data suggest that asymptomatic early dissemination occurs up to 44% of the time and that mild early disseminated disease is effectively treated with 3 weeks of oral antibiotics, the author prefers this longer duration. However, one study found no significant difference between 10 days of treatment and 20 days of treatment.⁵ Good data suggest that patients with multiple (secondary) EM or facial palsy without meningitis fare as well with 21 days of oral doxycycline therapy as they do with 14 day of intravenous ceftriaxone therapy. Patients with meningitis, radiculoneuritis, and a high-grade atrioventricular block should be treated with intravenous regimens. A few physicians believe that longer-term parenteral antibiotics are needed for refractory cases.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting. Consider coverage for co-infecting organisms, such as Ehrlichia species.

FOLLOW-UP

Section 8 of 11  

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• Introduction
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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Further Inpatient Care

• The stages of Lyme disease that the ED physician normally sees rarely require inpatient care. Two noteworthy caveats must be considered.
• • Patients with Lyme meningitis may need to be admitted not only for pain control but also for administration of intravenous antibiotics. In addition, if diagnostic uncertainty exists regarding the etiology of the meningitis, the antibiotic coverage may need to be extended for other more serious bacterial pathogens until the precise etiology is clarified.
  • The patient with myocarditis generally is not very ill, and significant muscle dysfunction is unusual. Pericarditis with tamponade, while rare, has been reported. Perhaps of greatest importance, recognize that Lyme carditis is a reversible cause of complete heart block and rarely requires a permanent pacemaker; therefore, consider Lyme disease in patients with a third-degree heart block (in the appropriate epidemiologic circumstances). These patients require admission to a telemetry unit.

Further Outpatient Care

• Patients with Lyme disease can have other manifestations in the future, especially if the disease is diagnosed late or if the patient is noncompliant with antibiotic therapy. Also, treatment failures have been reported with virtually every antibiotic regimen. Furthermore, serologic test results for Lyme disease are not available in time for care in the ED. Also, manifestations may be slow to resolve.
• • For these reasons, follow-up is imperative, preferably with a primary care physician.
  • The individual clinical situation determines the timing of the follow-up visit.

Deterrence/Prevention

• Vaccination is one preventative measure.
• • In 1998, results of 2 large trials of vaccines directed toward the outer surface protein A (Osp A) were reported. One product (LYMErix, SmithKline Beecham) received the approval of the US Food and Drug Administration in December 1998, for use in the prevention of Lyme disease. However, because of poor demand for the product, the sale was later discontinued in the United States (2002). The original trial included nonpregnant patients aged 15-70 years, with 3 doses administered on a 0-, 1-, and 12-month schedule. Newer data suggest that a 0-, 1-, and 2-month dosing schedule is equally effective.
  • After 2 doses of vaccine, a protection rate of only about 50% protection rate was present; after the third dose, roughly 80% of the patients developed protective antibodies.
  • At the present time, no human vaccine for Lyme disease is on the market in North America.
  • Vaccinated individuals have positive results with enzyme-linked immunoassays for Lyme antibodies but can be distinguished on the basis of a Western blot test.
• For other information about the prevention of tick-borne diseases, see Tick-borne Diseases, Introduction.
• See Emergency Department Care for tick bite prophylaxis.

Complications

• Lyme disease initially misdiagnosed or treated late may progress to harder-to-treat disease with some symptoms, especially neurologic, that can be debilitating. Thus, the emergency physician must be aware of Lyme disease and must promptly initiate treatment or refer patients to their primary care physician or other physician for appropriate antibiotic therapy; specific care depends on specific details of the situation.
• Third-degree heart blocks often require a temporary pacemaker insertion and, on rare occasions, a permanent pacemaker insertion.
• Doxycycline can cause severe cutaneous photosensitivity. Caution patients to use sunblock with an SPF of at least 30 and to wear wide-brimmed hats for further protection.
• A primary care physician should follow-up patients receiving long-term intravenous ceftriaxone, because biliary colic can develop from the sludge that forms secondary to this therapy.
• Some genetically predisposed patients develop chronic arthritis that is driven by immunopathogenic mechanisms and not active infection. This situation is resistant to antibiotics.
• In some studies, as many as 10-15% of patients with Lyme disease have been co-infected with another tick-borne pathogen. Therefore, consider this possibility if the disease does not respond as expected with ordinary early Lyme disease. Evidence suggests that co-infected patients have more symptoms of longer duration compared with other patients. In addition, these patients may be sicker than others on first observation. Also, implications exist for choice of antibiotics.

Prognosis

• Several studies report an excellent prognosis for patients who are promptly treated for early Lyme disease. As in most diseases, the earlier treatment begins, the better the results.
• Patients with late disease may have symptoms that are hard to eradicate. Also, these symptoms tend to disappear more slowly than do early symptoms. Controversy exists regarding the best therapy for these patients.
• The types of syndromes that emergency physicians generally treat, which is to say the early ones, respond well.

Patient Education

• Educate patients about tick avoidance and proper tick removal. For details, see Tick-borne Diseases, Introduction. This is very important since one episode of EM does not always confer immunity to the next. The same type of activity that led to the tick bite in the first place may still be occurring.
• Educate patients with early stages of Lyme disease about symptoms that can develop later. Development of these symptoms necessitates re-examination and may indicate treatment failure or incorrect diagnosis.
• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to diagnose several tick-borne diseases, including Lyme disease, is a pitfall.
• A related pitfall is a failure to consider Lyme disease because of the absence of a known tick bite. Only about 25-30% of patients with Lyme disease recall the bite. Far more importantly, inquire about activities that may increase the patient's risk for tick bites.
• Another pitfall is a failure to consider Lyme disease because of the absence of central clearing in a patient with EM. This classic finding of clearing occurs in only a minority of patients and is not needed for making the diagnosis.
• Patients with Lyme disease may be co-infected with other organisms, especially Ehrlichia and Babesia species. Patients with definite Lyme disease and symptoms such as higher fever or atypical manifestations (eg, leukopenia) may have such co-infections and require different therapies. Co-infections occur in roughly 10-15% of patients with Lyme disease.
• Remember the limitations of the serologic tests for Lyme disease. Results can be false positive or false negative. Misinterpretation of results can lead to serious problems. This is especially true in early presenting patients and in those with asymptomatic tick bites. Those with EM often have negative serologic test results. If EM is the likely diagnosis, empiric treatment, not serologic testing, is the appropriate action.

Special Concerns

• Avoid tetracyclines in pregnant patients and in those younger than 9 years.
• Have a lower threshold for prophylaxis in pregnant women with asymptomatic tick bites.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  This patient's erythema migrans rash demonstrates several key features of the rash, including size, location, and presence of a central punctum, which can be seen right at the lateral margin of the inferior gluteal fold. Note that the color is uniform; this pattern probably is more common than the classic pattern of central clearing.
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Media file 2:  The thorax and torso are typical locations for erythema migrans. The lesion is slightly darker in the center, a common variation. In addition, this patient worked outdoors in a highly endemic area. Physical examination also revealed a right axillary lymph node.
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Media file 3:  This patient recalled pulling a tick from the left side of his neck 7 days previously. His rash displays the vesicular variant. Roughly 18 hours after the first dose of doxycycline, he developed a typical Jarisch-Herxheimer reaction.
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Media file 4:  The Ixodes scapularis tick is considerably smaller than the Dermacentor tick. The former is the vector for Lyme disease, granulocytic ehrlichiosis, and babesiosis. The latter is the vector for Rocky Mountain spotted fever. This photo displays an adult I scapularis tick (on the right) next to an adult Dermacentor variabilis; both are next to a common match displayed for scale. Photo by Darlyne Murawski; reproduced with permission.
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Media file 5:  In general, Ixodes scapularis must be attached for 24-48 hours to transmit the spirochete to the host mammal. Prophylactic antibiotics are more likely to be helpful if feeding is longer. This photo shows 2 I scapularis nymphs. The one on the right is unfed; the other has been feeding for 48 hours. Note its larger size and the fact that the midgut diverticula (delicate brown linear areas on the body) are blurred. Photo by Darlyne Murawski; reproduced with permission.
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Media file 6:  This is the classic target lesion of erythema migrans (EM). Although this morphology has been emphasized in the older literature, in North America, it represents only about 40% of all EM lesions. This morphology is more commonly found in Europe. Photo reproduced with permission; Lyme Disease Foundation, Hartford, CT.
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Media file 7:  Lyme disease frequently affects children. Pictured below is a young girl with no known tick bite in the area. While vacationing with her family on Fire Island in August, this young girl developed the rash shown below. She was treated successfully with amoxicillin. Photo courtesy of Dr John Hanrahan.
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Media file 8:  This is an ECG from a 21-year-old man with severe weakness and near syncope. Ten days earlier, while in upstate New York, he had a febrile illness without rash. No tick bite was known to occur, and the serologic result for Lyme disease was negative at the time. Seroconversion occurred when this ECG was obtained. He was admitted to a telemetry unit, had a temporary pacemaker inserted, and was given 2 g of intravenous ceftriaxone daily. He was well and did not need the pacemaker after 4 days.
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Media file 9:  This patient from Nantucket presented in early July with this rash. When the rash started, he had been treated for 1 week with Lotrisone for a presumed tineal infection, but the initial lesion grew, and new ones developed. He worked outside as a carpenter but had no definite tick bite.
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Media file 10:  This patient from a highly endemic area presented in July with a lesion on his ankle. It was mildly painful and had been present for 2-3 days. Mild tenderness was evident on physical examination. Both cellulitis and erythema migrans were possibilities; therefore, the patient was treated for both. Cefuroxime axetil or amoxicillin-clavulanate is useful in this situation because of their antimicrobial spectra.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Wormser GP, McKenna D, Carlin J, et al. Brief communication: hematogenous dissemination in early Lyme disease. Ann Intern Med. May 3 2005;142(9):751-5. [Medline].
2. Nadelman RB, Nowakowski J, Forseter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med. May 1996;100(5):502-8. [Medline].
3. Nadelman RB, Nowakowski J, Fish D. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. Jul 12 2001;345(2):79-84. [Medline].
4. Dattwyler RJ, Luft BJ, Kunkel MJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med. Jul 31 1997;337(5):289-94. [Medline].
5. Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. May 6 2003;138(9):697-704. [Medline].
6. Brown SL, Hansen SL, Langone JJ. Role of serology in the diagnosis of Lyme disease. JAMA. Jul 7 1999;282(1):62-6. [Medline].
7. Edlow JA. Bull's Eye - Unraveling the Medical Mystery of Lyme Disease. 2nd ed (paperback). Yale University Press; 2004.
8. Edlow JA. Erythema migrans. Med Clin North Am. Mar 2002;86(2):239-60. [Medline].
9. Edlow JA. Lyme disease and related tick-borne illnesses. Ann Emerg Med. Jun 1999;33(6):680-93. [Medline].
10. Feder HM Jr, Whitaker DL. Misdiagnosis of erythema migrans. Am J Med. Oct 1995;99(4):412-9. [Medline].
11. Fish D. Environmental risk and prevention of Lyme disease. Am J Med. Apr 24 1995;98(4A):2S-8S; discussion 8S-9S. [Medline].
12. Krause PJ, Telford SR 3rd, Spielman A, et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. Jun 5 1996;275(21):1657-60. [Medline].
13. Luft BJ, Steinman CR, Neimark HC, et al. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. JAMA. Mar 11 1992;267(10):1364-7. [Medline].
14. Philipp MT, Wormser GP, Marques AR, et al. A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated