Lyme disease is a multisystem illness caused by the spirochete Borrelia burgdorferi sensu lato. It is a vector-borne disease transmitted to humans by infected ticks of the Ixodes genus. Lyme disease is the most common vector-borne illness in the United States, accounting for 30,158 reported cases in 2010. It is also endemic in the rest of North America, Europe, and Asia.[1]
View Image
Normal and engorged Ixodes ticks.
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.[2]
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.[3, 4] 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 plasma 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.[5] 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.
Data published in November 2008 show that some genotypes of B burgdorferi are responsible for the large majority of cases of disseminated disease.[6] At the present time, this information likely has greater significance for future vaccines or diagnostic tests than it does in routine practice.
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.
Phases of Lyme disease
The course of Lyme disease was initially described as being in stages, ie, I, II, III, but this was later revised as occurring in 3 phases: Early Lyme disease, early disseminated Lyme disease, and late Lyme disease. This is a more accurate naming system because the disease does not have multiple, distinct, and separated stages.
The early localized phase generally occurs within 30 days of the tick bite. Most patients present with a characteristic expanding rash (erythema migrans) at the site of the tick bite 7-14 days after the tick is removed. Several other nonspecific symptoms can occur and include fatigue, myalgias, arthralgias, headache, fever, chills, and neck stiffness.
The early disseminated disease generally occurrs weeks to months after the bite. Musculoskeletal and neurologic symptoms are the most common; less common symptoms are cardiac and dermatologic.
Late or chronic Lyme disease happens months to years after infection, which sometimes involves a period of latency. Musculoskeletal (mainly joints) and neurologic systems are most commonly affected.
In January 2008, the Council of State and Territorial Epidemiologists (CSTE) approved a revised national surveillance case definition for Lyme disease. This allowed for the addition of probable cases to the total case count, which differs from previous years.
Overall in the United States, incidence is 9.21-11.67 cases per 100,000 population (2007 and 2008 data). The total number of reported cases in 2010 in the United States was 30,158 (including 22,561 confirmed and 7,597 probable cases).
The total number of cases has been increasing over time. The total number of cases in 1995, 2000, 2005, and 2010 were 11,700, 17,730, 23,305, and 30,158, respectively. The increase in incidence is not simply a result of increased recognition; 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.[1]
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.
The risk of Lyme disease follows a general geographic pattern. Approximately 95% of confirmed Lyme disease cases are reported from states in the Northeast, mid Atlantic, and upper Midwest. A rash that can be confused with early Lyme disease sometimes occurs following bites of the lone star tick (Amblyomma americanum). These ticks, which do not transmit the Lyme disease bacterium, are common human-biting ticks in the southern and southeastern United States.
More than 90% of cases come from 10 states: Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin.[7]
Lyme disease risk in the United States is shown in the map below.
View Image
Lyme disease. Map of the United States presenting the incidence per 100,000 population of Lyme disease cases in each county in 2010. Courtesy of the U....
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, with 5 deaths reported in the United States in 2006.[1] Some fatal cases occur in patients who were simultaneously co-infected with other tick-borne pathogens such as Ehrlichia species and B microti, and in Europe, tick-borne encephalitis.
Morbidity is usually neurologic and rheumatic. Patients with neurologic disease who are not diagnosed and treated promptly can suffer from neurologic and cognitive dysfunction that can be difficult to treat. Some patients may have fixed neurologic deficits that are unresponsive to antibiotics. Patients with cardiac disease rarely exhibit chronic morbidity from their heart involvement. Similarly, some genetically predisposed individuals with arthritis may have ongoing joint inflammation that is not responsive 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
Males account for a slightly higher percentage of cases of Lyme disease, owing to an increase in males to tick exposure.
Age
As with other tick-borne diseases, the incidence of Lyme disease has a bimodal distribution with respect to age. Rates are highest among children aged 5-9 years and among adults aged 55-59 years. This distribution is also a function of tick exposure, rather than age.
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. Though imperfect, the various stages if Lyme disase and the associated timeline are helpful.
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. Nausea and vomiting are reported.
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. This rash is shown in the image below.
View Image
This is the classic target lesion of erythema migrans (EM). Although this morphology has been emphasized in the older literature, in North America, it....
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.[8]
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.
In an analysis of 313 children with facial palsy, 34% were due to Lyme disease. Clinical predictors were onset of symptoms between June to October, absence of herpetic lesions, presence of fever, and history of headache.[9]
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.[10]
Chest pain and dyspnea can occur in the setting of Lyme pericarditis, myocarditis, and myopericarditis. Cardiac tamponade has been reported.
Joint involvement
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.
Ocular invovlement
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.
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, other findings are described below.
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).[11] 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.[3, 12]
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 (shown in the image below), hairline, areas near elastic bands in bra straps or underwear). In children, the scalp, face, and hairline are more common locations.
View Image
This patient's erythema migrans rash demonstrates several key features of the rash, including size, location, and presence of a central punctum, which....
View Image
The thorax and torso are typical locations for erythema migrans. The lesion is slightly darker in the center, a common variation. In addition, this pa....
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).[8]
Acrodermatitis chronicum atrophicans (shown in the image below) 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.
View Image
Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic ph....
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
Other signs can include splenomegaly, hepatomegaly, and regional lymphadenopathy.
Lyme disease is caused by infection with the spirochete, B burgdorferi, the complete genome of which has been described recently. B burgdorferi is shown in the image below.
View Image
The bacterium Borrelia burgdorferi (darkfield microscopy technique, 400X; courtesy of the US Centers for Disease Control and Prevention).
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.[2, 13]
Laboratory testing depends entirely on the presenting problem of the patients.[14] 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.
Diagnosis
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.
Timing is extremely important. Seroconversion may take several weeks in patients infected with the spirochete, so early seronegativity is to be expected.
Laboratory criteria for diagnosis are as follows:
For the purposes of surveillance, the definition of a qualified laboratory assay is
Positive culture for B burgdorferi, or
Two-tier testing interpreted using established criteria, where positive immunoglobulin M (IgM) is sufficient only when 30 days or less from symptom onset or positive immunoglobulin G (IgG) is sufficient at any point during illness
Single-tier IgG immunoblot seropositivity using established criteria
CSF antibody positive for B burgdorferi by enzyme immunoassay (EIA) or immunofluorescence assay (IFA), when the titer is higher than it was in serum[15]
The US Centers for Disease Control and Prevention (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. It is important to test the proper patient population and to be able to interpret the results.
Understanding testing and test results
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 in whom 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. In addition, a small percentage of the healthy population has positive test results with ELISA testing. For these reasons, confirmatory Western blot testing is recommended.
On the other hand, patients with prior Lyme disease may have persistently positive results. In addition, vaccinated patients 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. Finally, 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.
Culture testing
Because of the fastidious growth requirements for B burgdorferi, 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.[14]
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 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.
Head CT may be warranted in patients with altered mental status, neurological findings, and/or neurological complaints.
Radiography may also be the initial imaging study of choice in patients with joint pain.
ECG testing is indicated for patients with an abnormal heart rate or cardiac complaints.
In the last few years, research on newer serologic tests—specifically the C6 peptide and the VlsE—is promising. These test results may well turn positive earlier and revert to negative after successful treatment. In July 2008, investigators published a prospective comparison between the standard 2-tier testing and an IgG of the VlsE of the C6 peptide. They found that both tests were sensitive, but the 2-tier testing had slightly better specificity.[16] The current CDC recommended 2-tier testing remains the preferred method in routine practice, and serological testing is still not recommended for patients with erythema migrans.
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 (LP) in patients with EM and any CNS symptoms or in patients with isolated seventh nerve palsy due to Lyme disease. They do this with the notion that an elevated protein level or pleocytosis mandates parenteral therapy.
A 2008 study randomized 118 European patients with CNS lyme to 2 weeks of oral doxycycline versus parenteral ceftriaxone therapy.[17] They found that clinical outcomes were the same in both groups, indicating that an LP may not be necessary if the purpose is to decide on route of therapy. Because of the differences in causative borrelial species, it is not clear if this finding is relevant to North American patients.
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.
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. That said, it makes sense to start antimicrobial therapy in the ED, or with a prescription to be filled upon leaving the ED.
The following clinical guidelines are the latest recommendations from the Infectious Diseases Society of America. Clinical guidelines are available from the American Academy of Neurology, Infectious Diseases Society of America, and International Lyme and Associated Diseases Society.[18, 19, 20]
See the tables below.
Table 1. Clinical Presentation and Therapy for the Phases of Lyme Disease
View Table
See Table
Table 2. Adult and Pediatric Treatment Options, Dosages, and Routes of Administration
View Table
See Table
Tick bite without other symptoms or signs
For prevention of Lyme disease after a recognized tick bite, routine use of antimicrobial prophylaxis or serologic testing is not recommended. A single dose of doxycycline may be offered to adult patients (200 mg dose) and to children older than 8 years (4 mg/kg, up to a maximum dose of 200 mg) when all of the following circumstances are present:[19]
The attached tick can be reliably identified as an adult or nymphal I scapularis tick that is estimated to have been attached for longer than 36 hours on the basis of the degree of engorgement of the tick with blood or of certainty about the time of exposure to the tick
Prophylaxis can be started within 72 hours of the time that the tick was removed
Ecologic information indicates that the local rate of infection of these ticks with B burgdorferi is more 20%
Doxycycline treatment is not contraindicated
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.[21] It also corroborated the finding that duration of attachment is an important marker for transmission.
Amoxicillin should not be substituted for doxycycline in persons for whom doxycycline prophylaxis is contraindicated because of the absence of data on an effective short-course regimen for prophylaxis, the likely need for a multiday regimen (and its associated adverse effects), the excellent efficacy of antibiotic treatment of Lyme disease if infection were to develop, and the extremely low risk that a person with a recognized bite will develop a serious complication of Lyme disease.
Solitary EM
Doxycycline, amoxicillin, or cefuroxime axetil for 14 days (range, 10–21 d for doxycycline and 14–21 d for amoxicillin or cefuroxime axetil) is recommended for the treatment of adult patients with early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic manifestations or advanced atrioventricular heart block. Each of these antimicrobial agents has been shown to be highly effective for the treatment of erythema migrans and associated symptoms in prospective studies. Treatment duration was previously recommended to be longer, but several studies have shown similar efficacy between 10-day and longer courses (20-21 d).[22, 23]
Antibiotics recommended for children include amoxicillin, cefuroxime axetil, or, if the patient is older than 8 years, doxycycline may be used.
Macrolide antibiotics are not recommended as first-line therapy for early Lyme disease, because those macrolides that have been compared with other antimicrobials in clinical trials have been found to be less effective. When used, they should be reserved for patients who are intolerant of, or should not take, amoxicillin, doxycycline, and cefuroxime axetil.
Lyme meningitis and other manifestations of early neurologic Lyme disease
The use of ceftriaxone in early Lyme disease is recommended for adult patients with acute neurologic disease manifested by meningitis or radiculopathy. Possible satisfactory alternatives include parenteral therapy with cefotaxime or penicillin G. For patients who are intolerant of β-lactam antibiotics, increasing evidence indicates that oral doxycycline (200–400 mg/d in 2 divided doses orally for 10–28 d) may be adequate.
Lyme carditis
Patients with atrioventricular heart block and/or myopericarditis associated with early Lyme disease may be treated with either oral or parenteral antibiotic therapy for 14 days (range, 14–21 days). Hospitalization and continuous monitoring are advisable for: (1) symptomatic patients, such as those with syncope, dyspnea, or chest pain; (2) patients with second-degree or third-degree atrioventricular block; (3) patients with first-degree heart block when the PR interval is prolonged to more than 30 milliseconds (because the degree of block may fluctuate and worsen very rapidly in such patients).
For patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended. Use of the pacemaker may be discontinued when the advanced heart block has resolved. An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis.
Arthritis
Lyme arthritis can usually be treated successfully with antimicrobial agents administered orally, with an extended treatment time of 28 days. For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, it is recommended re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of ceftriaxone IV.
Late neurologic Lyme disease
Adult patients with late neurologic disease affecting the central or peripheral nervous system should be treated with IV medication. Response to treatment is usually slow and may be incomplete. Retreatment is not recommended unless relapse is shown by reliable objective measures.
Pregnancy
Pregnant and lactating patients may be treated in a fashion identical to nonpregnant patients with the same disease manifestation, except that doxycycline should be avoided.
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.
Early Lyme disease usually responds well to antibiotics, with regimens shown above. Data regarding the route and duration of therapy are evolving and are, to some extent, controversial.
Clinical Context:
Treats infections caused by susceptible organisms. PO DOC for pediatric patients < 9 y. Duration of therapy depends on specific disease manifestations.
Clinical Context:
PO DOC for adults. Key advantage of covering other tick-borne pathogens that may have been cotransmitted (eg, Ehrlichia species, Rickettsia species). Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.
Clinical Context:
Only FDA-approved drug for Lyme disease, but it is a second-line drug for economic reasons. Condition of patient, severity of infection, and susceptibility of microorganism determines proper dose and route of administration.
Clinical Context:
Third-generation cephalosporin that is the IV DOC. Excellent activity against B burgdorferi and has favorable pharmacokinetics. Inhibits bacterial cell wall synthesis by binding to one or more penicillin-binding proteins. Bacteria eventually lyse because of ongoing activity of cell wall autolytic enzymes, while cell wall assembly is inhibited.
Clinical Context:
Useful drug but must be administered 6 times/d. Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.
Clinical Context:
Treats susceptible bacterial infections of gram-positive and gram-negative organisms, as well as infections from Rickettsia species. Also effective against ehrlichiosis. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Clinical Context:
Mixed data exist regarding use in early Lyme disease. While one large, randomized North American study showed azithromycin to be inferior to amoxicillin, treatment duration in the 2 groups were not equal, even when the prolonged half-life of azithromycin was considered. At least 5 other smaller studies have revealed that it was as effective as other antibiotics tested. This is not a first- or second-line drug but could be useful in some situations.
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.
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.
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.
Lyme disease prevention has focused traditionally on reducing human exposure to the bites of infected ticks. Current recommendations include practices such as the following:[24]
Avoiding tick-infested areas
Using insect repellants
Wearing light-colored clothing on which ticks are more readily detected
Wearing long trousers and tucking them into socks to keep ticks on outer clothing
Performing bodily tick checks, followed by prompt tick removal
Landscape management
Acaricide applications on property or targeted to hosts
Management of deer populations
Vaccination
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.[25] Newer data suggest that a 0-month, 1-month, 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. Vaccinated individuals have positive results with enzyme-linked immunoassays for Lyme antibodies but can be distinguished on the basis of a Western blot test.
At the present time, no human vaccine for Lyme disease is on the market in North America.
For other information about the prevention of tick-borne diseases, see Tick-borne Diseases, Introduction. See Emergency Department Care for tick bite prophylaxis.
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.
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.
William E Caputo, MD, Chief Resident Physician, Department of Emergency Medicine, Kings County Hospital
Disclosure: Nothing to disclose.
Coauthor(s)
Richard H Sinert, DO, Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Disclosure: Nothing to disclose.
Specialty Editors
Dan Danzl, MD, Chair, Professor, Department of Emergency Medicine, University of Louisville Hospital
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Jon Mark Hirshon, MD, MPH, Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine
Disclosure: Nothing to disclose.
John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Rick Kulkarni, MD, Attending Physician, Department of Emergency Medicine, Cambridge Health Alliance, Division of Emergency Medicine, Harvard Medical School
Disclosure: WebMD Salary Employment
Additional Contributors
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Jonathan A Edlow, MD, to the development and writing of this article.
Lyme disease. Map of the United States presenting the incidence per 100,000 population of Lyme disease cases in each county in 2010. Courtesy of the US Centers for Disease Control and Prevention.
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.
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.
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.
Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic phase. As the term suggests, the lesion occurs acrally and ultimately results in skin described as being like cigarette paper. Courtesy of Lyme Disease Foundation, Hartford, Conn.
The bacterium Borrelia burgdorferi (darkfield microscopy technique, 400X; courtesy of the US Centers for Disease Control and Prevention).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ticks are the most common vectors for vector-borne diseases in the United States. In North America, tick bites can cause Lyme disease, human granulocytic and monocytic ehrlichiosis, babesiosis, relapsing fever, Rocky Mountain spotted fever, Colorado tick fever, tularemia, Q fever, and tick paralysis. Europe has a similar list of illnesses caused by ticks, but additional concerns include boutonneuse fever and tick-borne encephalitis. Lyme disease is one of the most prominent tick-borne diseases, and its main vector is the tick genus Ixodes, primarily Ixodes scapularis. Image courtesy of the US Centers of Disease Control and Prevention.
The bacterium Borrelia burgdorferi (darkfield microscopy technique, 400X; courtesy of the US Centers for Disease Control and Prevention).
Approximate US distribution of Ixodes scapularis. Image courtesy of the US Centers for Disease Control and Prevention.
Amblyomma americanum is the tick vector for monocytic ehrlichiosis and tularemia. An adult and a nymphal form are shown (common match shown for size comparison). Image by Darlyne Murawski; reproduced with permission. Ehrlichiosis is a tick-borne infection of the white blood cells caused by Ehrlichia species. Typical symptoms include fever, headache, malaise, and myalgia, and they occur 5-14 days after the tick bite. It is sometimes referred to as "spotless" Rocky Mountain spotted fever. The treatment of choice is doxycycline, 100 mg twice daily, either orally or intravenously for 10 days. This regimen will also treat Lyme disease and the often mistaken Rocky Mountain spotted fever. Rifampin, 200 mg twice daily for 7 days, is a second-line option because chloramphenicol does not treat Ehrlichia chaffeensis. Tularemia is a zoonosis caused by infection with Francisella tularensis. Typical symptoms include fever, lethargy, anorexia, and in some forms, extensive ulcerating lymphadenopathy. With early diagnosis and treatment, mortality is rare (1%). Antibiotic treatment with streptomycin, 1 g intramuscularly twice daily for 10 days, eradicates the bacteria.
Approximate US distribution of A americanum. Image courtesy of the US Centers for Disease Control and Prevention.
The soft-bodied tick of the genus Ornithodoros transmits various Borrelia species that cause relapsing fever. Photo courtesy of Julie Rawlings, MPH, Texas Department of Health. Relapsing fever is characterized by recurrent acute episodes of fever (usually >39°C). It is a vector-borne illness spread by lice and ticks. The spirochete species Borrelia is responsible. For tick-borne relapsing fever, treatment is with tetracycline, 500 mg orally every 6 hours, or doxycycline, 100 mg orally twice daily, for 10 days. The louse-borne illness usually only requires a single dose of tetracycline or erythromycin, 500 mg orally.
Approximate US distribution of Dermacentor andersoni. Image courtesy of the US Centers for Disease Control and Prevention.
Rhipicephalus ticks are vectors for babesiosis and rickettsial infections, among others. Image courtesy of Dirk M. Elston, MD. In typical practice, testing ticks for tick-borne infectious organisms is not generally recommended. However, healthcare practitioners should become familiar with the clinical manifestations of tick-borne diseases (eg, Lyme disease, especially those practicing in endemic areas) and maintain a high index of suspicion during warmer months. Ticks can be placed in a sealed container with alcohol if they need to be transported and identified.
A rarely reported noninfectious complication for tick bites is alopecia. It can begin within a week of tick removal and typically occurs in a 3- to 4-cm circle around a tick bite on the scalp. A moth-eaten alopecia of the scalp caused by bites of Dermacentor variabilis (the American dog tick) has also been described. No particular species appears more likely to cause alopecia. Hair regrowth typically occurs within 1-3 months, although permanent alopecia has been observed.
To remove a tick, use fine-tipped forceps and wear gloves. Grasp the tick as close to the skin surface as possible, including the mouth parts, and pull upward with steady, even traction. Do not twist or jerk the tick because this may cause the mouth parts to break off and remain in the skin; however, note that the mouth parts themselves are not infectious. When removing, wear gloves to avoid possible infection. Children, elderly persons, and immunocompromised persons may be at greater risk for infection and should avoid removing ticks if possible. A common misperception is that pressing a hot match to the tick or trying to smother it with petroleum jelly, gasoline, nail polish, or other noxious substances is beneficial. This only prolongs exposure time and may cause the tick to eject infectious organisms into the body. Additionally, using lidocaine (subcutaneously or topically) may actually irritate the tick and prompt it to regurgitate its stomach contents. Finally, do not squeeze, crush, or puncture the body of the tick because its fluids (saliva, hemolymph, gut contents) may contain infectious organisms. Once the tick is removed, wash the bite area with soap and water or with an antiseptic to destroy any contaminating microorganisms. Additionally, the person who removed the tick should wash his or her hands.
Tick-borne disease prevention can be divided into environmental and personal measures. Patients exposed to tick-endemic areas should wear long-sleeved, light-colored clothing when outside. Lighter colors allow for easier identification of ticks. Chemical repellents with DEET (N,N-diethyl-3-methylbenzamide) and picaridin are available in numerous over-the-counter skin preparations as sprays or lotions. Permethrin is an acaricide that can be applied to clothing and is used in conjunction with chemical repellents. All individuals should perform regular skin checks. Ticks prefer warm, moist areas, such as the beltline, groin, and axilla, although in children, the hairline is a common site. Environmental prevention involves clearing underbrush and spraying acaricides in the spring around property sites. These measures prevent both mice and ticks from encroaching on properties. Studies involving the treatment of wild deer and mice have not been conclusive in reducing tick-borne diseases in humans. Currently, no Lyme disease vaccines are available in the United States. Lyme disease vaccine (Lymerix™) was discontinued in 2002, so some patients may still have residual protective antibodies. Image courtesy of the National Library of Medicine.
Hematoxylin and eosin stained section from a biopsy performed at the periphery of an eruption. Note the perivascular lymphocytic infiltrate, a pattern that is not specific for, but is characteristic of, erythema migrans.
Borrelial lymphocytoma of the earlobe, which shows a bluish red discoloration. The location is typical in children, as opposed to the nipple in adults. This manifestation of Lyme disease is uncommon and occurs only in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn.
Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic phase. As the term suggests, the lesion occurs acrally and ultimately results in skin described as being like cigarette paper. Courtesy of Lyme Disease Foundation, Hartford, Conn.
Multiple lesions of erythema migrans occur in approximately 20% of patients. This patient, a carpenter from Nantucket who worked predominantly outside, had been treated with Lotrisone for 1 week prior to presenting to the emergency department with this rash. The patient had no fever and only mild systemic symptoms. He was treated with a 3-week course of oral antibiotics.
Blood smear showing likely babesiosis. Babesiosis can be difficult to distinguish from malaria on a blood smear.
Magnified ticks at various stages of development.
Typical appearance of erythema migrans, the bull's-eye rash of Lyme disease
Lyme rash. Courtesy of M. Fergione, B. Tucker, and L. Zernel; Pfizer Laboratories.
Normal and engorged Ixodes ticks.
Erythema migrans, the characteristic rash of early Lyme disease.
Bulls-eye rash
Lyme disease. Map of the United States presenting the incidence per 100,000 population of Lyme disease cases in each county in 2010. Courtesy of the US Centers for Disease Control and Prevention.
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}