Emergency Medicine Reports May 26, 1997

The Multiple Faces of Lyme Disease and Other Common Tick-Borne Conditions: Diagnostic Challenges and Management Considerations

Author: Jonathan A. Edlow, MD, Associate Director, Department of Emergency Medicine, Mount Auburn Hospital, Cambridge,MA; Clinical Director, Division of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Instructor in Medicine, Harvard Medical School, Cambridge, MA.

Peer Reviewer: Frank J. Edwards, MD, FACEP, Medical Director, Division of Community and Rural Emergency Medicine, Greater Rochester Health System; Clinical Assistant Professor of Emergency Medicine, University of Rochester, Rochester, NY.

With the thaws and blossoms of spring arrive other, less-welcome offerings of nature: ticks and their propensity for producing an eclectic range of serious and sometimes life-threatening disorders. Human tick-borne diseases (TBD), which can cause significant morbidity and mortality in all age ranges, represent an important diagnostic challenge for emergency physicians, especially during the summer months.

Not surprisingly, clinical presentations for tick-related infections are highly variable. Signs, symptoms, and target organ damage can result from myriad mechanisms, including non-infectious inflammatory responses (hypersensitivity and toxin-mediated reactions), secondary bacterial infection associated with skin trauma, and primary inoculation into the skin of infectious agents that produce conditions ranging from babesiosis to Lyme disease (LD).

The most common vector-borne disease in the United States, LD was first described as a unified clinical entity in 1977 following an outbreak of statistically improbable childhood arthritis associated with a distinctive rash called erythema migrans (EM).1 The description and geographical spread of LD, the recognition of two forms of human ehrlichiosis, and a growing appreciation of domestic babesiosis have sparked a renewed interest in TBD over the last 20 years. These three diseases, caused by different classes of microorganisms, share a common tick vector, and their increased prevalence is at least in part related to changes in our environment and the way we relate to it. Expansion of the deer herd in the Northeast, the incursion of people into more rural habitats, and increased recognition of TBD all play a role.2,3

Patients with TBD frequently develop acute illness and seek care in the ED. Thus, clinicians must know when antimicrobial therapy is indicated, indications for serological testing, and clinical findings that require lumbar puncture or hospitalization. This report will focus primarily on the early manifestations of LD but will also describe clinical manifestations of Rocky Mountain spotted fever (RMSF), babesiosis, and ehrlichiosis. Diagnostic tests will be highlighted and vaccines will be mentioned.

—The Editor

Epidemiology and Infectious Patterns

LD is by far the most common TBD in the United States and has been reported in nearly every state. Over the past several years, about 10,000 annual cases have been reported to the CDC,4-6 though it is likely that 10 times that number occur.7 In 1995, LD was reported in 43 states, but its frequency is highly patchy, with eight states (Connecticut, New York, Rhode Island, New Jersey, Delaware, Maryland, Pennsylvania, and Wisconsin), accounting for more than 80% of cases.6 The seven states in which LD was not seen were Alaska, Hawaii, Colorado, Idaho, Montana, and North and South Dakota.

The incidence varies widely, from nine cases per 100,000 people in Maryland to 839 per 100,000 on Nantucket island off the Massachusetts coast. Even within a given state, incidence varies widely by county. The overall incidence in the United States is 4.4 per 100,000.6

As would be expected, people whose jobs or recreational activities expose them to ticks have an increased risk of acquiring TBD. There appears to be no sex or age predilection. Nevertheless, CDC data show a bimodal peak, with 24% of cases occurring in children younger than 15 and another 24% of cases in adults between 35 and 49 years of age.6 It should be emphasized that, in endemic areas, infected ticks can survive in well-maintained lawns.8,9 Infection with LD and other tick-borne diseases can also occur in urban areas.10

Clinical Manifestations: Three Phases

The likelihood of acquiring infection following a single tick bite is low.11,12 Following inoculation with Borrelia burgdorferi, the infecting organism of LD, three outcomes are possible with respect to the spirochete. First, the organisms can be completely eliminated by host defense mechanisms. Second, Borrelia can remain localized but viable in the skin.13,14 Last, they can disseminate to other organs via bloodstream or lymphatics. Dissemination can occur quite rapidly.15-17 With respect to clinical findings, B. burgdorferi appears to have a tropism for cutaneous, cardiac, nervous, and musculoskeletal tissues.18

From a practical, clinical perspective, LD has been divided into three stages: early localized disease (EM), early disseminated disease, and late disseminated disease. (See Table 1.) Typical late manifestations—including joint, skin, and nervous manifestations—occur many months to years after infection and are not discussed in this review. Asymptomatic patients presenting after tick bite will be discussed first.

Tick Bites: To Treat or Not to Treat

Tick-bite studies suggest that 24-48 hours of tick attachment is usually required for infection to occur.19-21 The time delay is explained by the fact that in most unfed ticks, the spirochetes are localized to the midgut. After the tick attaches to the host for a blood meal, the organisms migrate to the salivary glands, a journey that requires hours to days.22-24

Although many authors state categorically that more than 24 hours of attachment is required for transmission, clinical and experimental data suggest that transmission is clearly possible within a shorter duration, although the frequency of this occurrence in North America is unknown. In one European study of 231 culture-confirmed cases of EM, data were reported on those 34 patients who specifically recalled not only the tick bite but also the duration of attachment. In nine of the 34, the duration of attachment was less than six hours, and in an additional 16 of the 34, it was less than 24 hours.25 Moreover, clinical LD has also been documented after as little as six hours of attachment in North America.26 This probably occurs because some ticks are infected systemically, and these ticks could transmit the disease faster.

Endemic Areas. Several studies have examined the likelihood of developing clinical infection with B. burgdorferi in individuals who have had a tick bite in areas endemic for LD.11,12 Showing fairly consistent results, these studies demonstrate that 1-3% of patients develop the marker rash for EM after placebo treatment for a tick bite, even when the affected ticks had an infection rate of between 15-30%. Late symptoms or seroconversion were not seen in the placebo group. One possible methodological flaw in a larger study of over 300 patients was that serologic follow-up was only done at six weeks and three months.11,12 Only 75% of LD patients develop the marker rash of EM.27 While serologic conversion likely would have occurred within the three-month window, it is possible that some patients who never developed EM could have seroconverted after the three months and developed late disease after one year of clinical follow-up.

Treatment Considerations. Based on these investigations, the official recommendation is not to treat tick bites with prophylactic antibiotics. As a general rule, this represents a prudent, outcome-effective approach to clinical management. However, each case should be considered individually, and the clinical decision in the emergency-medicine setting should be based on a number of relevant risk factors, historical features, and physical findings.

Without question, duration of tick attachment is a critical parameter influencing the likelihood of acquiring clinical infection. Generally speaking, the longer the duration of attachment, the greater the likelihood of disease transmission. The species of biting tick is also important because, as a rule, only Ixodes ticks are capable of transmitting the disease. Characterizing the species of tick in the ED, however, may be difficult. The morphological stage of the tick should also be documented, since adult ticks are twice as likely to be infected as nymphs, and larvae are very rarely infected.3 Geography can play a decisive role in determining the need for emergency treatment. For example, in hyper-endemic areas, up to 50% of the Ixodes scapularis ticks can be infected, while in other areas, the rate is much lower.26,28

From a frontline, practical perspective, patient preference must enter into the management equation. Some patients, particularly those who live in endemic areas, are so anxious about acquiring LD that even after a thorough, reassuring explanation of the risks and options, a significant percentage will insist on antimicrobial prophylaxis and threaten go elsewhere if antibiotics are not prescribed. While there is no standard of "prophylactic" therapy for these situations, tick-bite studies that used a 10-day antibiotic course (amoxicillin in children, doxycycline in adults) have found no disease in the treatment groups.11,12

Early States of Lyme Disease: Localized Disease

Early localized LD refers to solitary EM, which is found in about 75% of infected patients.27 Classic EM starts as a red macule or papule that characteristically appears 1-33 days (average, 7-10) after the tick bite and expands centrifugally while clearing centrally.29 EM is generally flat, although the borders may be slightly raised. A central punctum resulting from the bite also may be present in some cases.30 Median size of the rash is 15-16 cm, but EM can attain a sizes up to 73 cm. 25,27,29

As a rule, the location of the rash reflects areas of the body where ticks frequently stop and feed, including the popliteal fossa, gluteal folds, groin, axilla, as well as areas where an elastic band of clothing presses against the skin. Despite a predilection for these sites, EM lesions can occur anywhere, though the hands and feet are distinctly unusual locations.25,27,29

The size of EM tends to be a function of the duration of infection. Typically, EM enlarges day by day, rather than over hours, and it does not remain stable over months. EM is associated with mild systemic symptoms such as fatigue, arthralgia, myalgia, headache, fever, chills, and stiff neck in about 40% of patients. Mild pruritis or pain sometimes accompanies the skin lesions.29

The emergency physician must be aware that atypical manifestations of EM are not uncommon and can include vesicular scaling and necrotic lesions.31 In addition, EM can occur in unusual shapes, and both linear and triangular configurations have been reported. EM can also be characterized by either central darkening or have a uniform color.25,27,29,32 EM can be mistaken for cellulitis, urticaria, contact dermatitis, tinea corporis, granuloma annulare, fixed drug eruption, and localized toxic or hypersensitivity reactions to arthropod bites.25,27,29,32-34 Finally, because few patients with LD recall their tick bite, a history of this event is not required for the diagnosis.

When EM findings are classical, the ED physician can confirm the diagnosis by performing a careful physical examination. In equivocal cases, the practitioner may elect to measure the lesion and then re-examine the patient in 2-3 days. The diagnosis of EM is suggested by a lesion that has expanded a few centimeters over this period, though it should be stressed that the features of evolving lesions can be extremely variable.31 Moreover, since EM can be evanescent—in fact, it will disappear after a few weeks even without antibiotic treatment—the clinician must be cautious when trying to draw definitive conclusions using this approach.

Although a culture of the advancing rim of the lesion will be positive in about 50-66% of cases, this microbiological test is not routinely available in most hospitals, and is not usually indicated.25,30,35 Complicating the diagnosis of LD is the fact that only 30-40% of patients are seropositive at this early stage of the illness. As a result, blood testing is not necessary in most cases.36 There are exceptions to this rule. In atypical or ambiguous cases, because most patients seroconvert by enzyme-linked immunosorbent assay (ELISA) test or IgM immunoblot even when treated promptly and appropriately, acute and convalescent testing can be of value in establishing the diagnosis.36

Early Disseminated Disease: Cutaneous and Systemic Manifestations

Disseminated hematogenously, multiple EM lesions are observed in about 20-50% of patients.25,27,29,32 The secondary lesions are generally smaller than the original lesion and lack a central punctum.30 Of special clinical, differential, and diagnostic significance is the fact that disseminated lesions tend to be found everywhere, except for palms, soles, and mucous membranes.31 Accordingly, accurate evaluation of these findings requires that the patient be fully unclothed.

A flu-like illness without a rash also occurs at this stage, though the incidence of this is unknown.37 This "spring or summer flu syndrome" can challenge the ED physician to distinguish among a number of conditions, ranging from trivial viral infections to several other tick-borne entities, including ehrlichiosis, babesiosis, and spotless Rocky Mountain spotted fever (RMSF), which can be fatal.

Because most patients with TBD are unaware of their tick bite, it is mandatory that the emergency physician not just ascertain whether a tick bite has occurred but whether one is likely to have occurred. Clues that suggest a tick bite include the season and participation in outdoor activities. Remember, however, that nothing more exotic than mowing the lawn or playing in the backyard is required.

Neurologic Manifestations. To reduce morbidity and improve patient outcomes, the ED physician must be able to recognize neurological signs and symptoms associated with LD. In this regard, it should be stressed that about 15-40% of untreated patients eventually develop neurologic sequelae that involve both the peripheral (PNS) and the central nervous system (CNS).18,38 The three common early neurologic syndromes that ED physicians must recognize present relatively early in the course of the disease (i.e., within weeks to months of the tick bite). These include lymphocytic meningitis, cranial neuropathy, and radiculoneuritis. Other reported neurological syndromes include acute myelitis, encephalitis, ataxia, and myositis.39 A pseudotumor cerebri-like syndrome has also been described in North American children.40 Timing of presentations is variable. Neurologic symptoms can precede the onset of EM, can occur without a prior history of EM, and can occur concurrently with the rash.41

Meningitis. Lyme meningitis results from direct invasion of the CNS by borrelial organisms.42 Symptoms, which are usually described as mild, are similar to those associated with other causes of meningeal irritation and include headache, stiff neck, and fatigue. Occasionally, patients have an element of mild encephalopathy and may present with such symptoms as forgetfulness and irritability.42 One clue to a borrelial etiology is symptoms that wax and wane over hours or days. Fever and severe meningismus are mild or absent.42 Otherwise, physical examination is unremarkable, unless a concurrent EM or seventh nerve palsy (7-NP) is present. Lumbar puncture shows lymphocytic pleocytosis and elevated protein. Collecting and saving extra CSF may be of subsequent value to the primary care physician, who may wish to perform other tests such as PCR and/or anti-B. burgdorferi antibodies at a later point in the clinical course.

As in all LD syndromes, a high index of suspicion and a careful history are the ED physician’s most powerful allies. Diagnosis is confirmed by culture in only about 5% of patients.42 Although most Lyme meningitis patients are seropositive, an occasional patient may be negative.42 There are many other etiologies for these symptoms. One Connecticut-based study of patients presenting with acute meningitis with a negative Gram’s stain of CSF found that only four patients of 168 had Lyme meningitis.43 In 71% of cases, a specific etiology was never established.

Cranial Neuropathy. Paralysis of the seventh cranial nerve is found in approximately 11% of patients with LD and is bilateral in 25% of cases.44 Paralysis of the second side generally occurs sequentially, days to weeks after the first. Bilateral 7-NP is an important clue to the diagnosis of LD, inasmuch as the other causes of bilateral 7-NP palsy (e.g., Guillain-Barré syndrome, neurosarcoidosis, and basilar meningitides like tuberculosis) are distinctly uncommon. In pediatric patients with 7-NP, LD needs to be excluded, as the idiopathic variety is less common in patients of this age group.45 One investigator reported that facial erythema and swelling is a clue that a 7-NP is borrelial in etiology and suggested that the 7-NP was frequently ipsilateral to the tick bite.46

The incidence of idiopathic Bell’s palsy is about 20 cases per 100,000 of population.47 In an endemic state like Connecticut, the incidence of LD is 46 per 100,000.6 If 11% of patients with LD get 7-NP, then the expected number of cases of 7-NP secondary to LD would be about 5 per 100,000 (or 20% of the total). Several studies have found incidence figures in this range, but others have not.47-51 Since idiopathic Bell’s palsy has no seasonal variance, 7-NP occurring during the summer months should be suspected of being borrelial in origin.

Although the majority of LD patients with 7-NP are seropositive, some patients are sero-negative. Hence, an initially negative serology does not rule out borrelial infection.47 Many clinicians advocate doing a lumbar puncture on these patients. The rationale is that patients with a pleocytosis should be treated with parenteral antibiotics, whereas those with normal CSF can be treated orally.18 Although this hypothesis does have some common-sense appeal, there are no controlled trials evaluating efficacy or clinical outcomes. Finally, the outcome of 7-NP in LD is excellent. In one early study of over 100 patients, not all of whom received antibiotics, the recovery rate was 99%.44

Radiculoneuritis. Radiculoneuritis appears to be more common in Europe (where it is known as Bennwarth’s syndrome) than in North America.38 This syndrome generally presents as a painful limb and may mimic the presentation of an acute herniated disc.39,52 The distribution of pain, however, is more characteristic of a plexitis, multiple radiculitis, or a mononeuritis multiplex.39,52 Like the other Lyme syndromes, these symptoms generally resolve without antibiotics after 5-6 months, but improve more quickly with antibiotic therapy.39

Cardiac Involvement. Fewer than 10% of untreated patients will develop cardiac manifestations of LD.18,53 On occasion, cardiac disease can even be the presenting feature. When it occurs, cardiac involvement generally presents weeks to months after the tick bite and is typically short-lived (days to weeks).53,54 Like most manifestations of LD, symptoms usually resolve spontaneously, even in the untreated patient. Symptoms include palpitations, light-headedness, syncope, dyspnea, and chest pain.53,55 Cardiac involvement is more common in men.53-55

Conduction abnormalities, especially varying degrees of atrio-ventricular (AV) block, are the most common cardiac manifestations, with complete, transient heart block occurring in about 50% of patients with cardiac involvement.53,55 Myocarditis, pericarditis, and myopericarditis also occur, and there is a single case report of pericarditis with tamponade.53-57

Despite the tendency for spontaneous improvement, anti-borrelial chemotherapy is indicated at this stage of disease, both to hasten resolution and to prevent progression of symptoms. Because patients with complete heart block from LD almost never require a permanent pacemaker, establishing the diagnosis is particularly important. Serologies are almost always, but not universally, positive at this stage of the illness.

Early Disseminated Syndromes

Ocular Syndromes. Ocular involvement occurs in the early and late stages of LD.58-60 Non-specific follicular conjunctivitis occurs in up to 10% of patients with early disease. Episcleritis and keratitis can be seen early in the disease, and blindness has been reported from panophthalmitis.57-61 The spirochete has been cultured from iris biopsy.62 Later stages of the disease include retinal vasculitis, inflammation of the retina, optic atrophy, and disc edema.58 Patients with ocular disease can be seronegative.59

Arthritis. Although classic Lyme arthritis is a late phenomenon, there are musculoskeletal manifestations that occur early in the natural history of the disease. Patients may experience migratory pains in muscles, tendons, joints, and bursae that may wax and wane over hours or days.63 Some patients will develop arthritis within weeks to months, which is usually is characterized by mono- or oligo-articular inflammation of large joints, typically the knee.

Hepatic. Liver involvement, suggested by abnormalities in the hepatic transaminases, is common.64 However, symptomatic hepatitis does not occur; splenomegaly develops occasionally.65,66

Other Tick-Borne Diseases: Differential Diagnosis

Ehrlichiosis. Caused by a rickettsial organism, two forms of human ehrlichiosis have been described: human granulocytic ehrlichiosis (HGE) and human monocytic ehrlichiosis (HME). HGE is common in geographical areas populated with I. scapularis ticks, while HME is transmitted by the lone-star tick (Amblyomma americanum), which predominates in the Southern and Midwestern states.67-69 Both entities present as a nonspecific febrile illness, with fever, chills, fatigue, headache, myalgias, and arthralgias. The accompanying rash can be macular, papular, or petechial.67-70 Adult respiratory distress syndrome has been reported with both HGE and HME.71,72

The diagnosis can be confirmed by the presence of berry-like inclusions called morulae in white blood cells on the peripheral smear. Morulae are found commonly in HGE, and rarely in HME. Associated diagnostic clues include leukopenia, thrombocytopenia (occasionally, pancytopenia), and elevated hepatic transaminases.67-69

From an emergency medicine perspective, the diagnosis is made on clinical grounds and requires a high index of suspicion. Making the diagnosis is important, inasmuch as ehrlichiosis is fatal in about 5% of cases, but can be treated with doxycycline.68,69,73

Babesiosis. Babesiosis is a protozoan disease that is carried by I. scapularis. It causes a non-specific febrile illness. Seroprevalence studies show that in endemic areas such as Block Island, up to 10% of individuals tested positive.74 One species of Babesia, B. microti, leads to a milder disease than that in Europe, where B. divergens frequently attacks asplenic patients and often leads to massive hemolysis, renal failure, and death.75 Domestic babesiosis is fatal in about 5% of patients.76

Symptoms of babesiosis are similar to those described above for ehrlichiosis.75,76 However, anemia is more likely to be encountered in babesiosis, which may also be accompanied by proteinuria and hemaglobinuria.75 The diagnosis can be made by examining a Giemsa-stained blood smear for intra-erythrocytic protozoa.75 Severe cases of babesiosis in asplenic patients, the immunocompromised, and the elderly are treated using a combination of clindamycin and quinine. Finally, studies indicate that co-infection of ehrlichiosis, babesiosis, or both can occur in combination with LD.77-82

Rocky Mountain Spotted Fever. RMSF also presents as a summer flu for the first three days and remains "spotless" in 10% of cases.83,84 Most patients, however, will exhibit a petechial rash on the third or fourth day of illness.84,85 Increased fatalities occur in RMSF patients who present during the first three days of symptoms, out of season, (October through April), and/or without a rash.86 Even with the much larger Dermacentor tick vector, 40% of RMSF victims do not recall the tick bite.85 Treatment with chloramphenicol or tetracycline has dramatically reduced the fatality rate from about 70% to roughly 5%.87

Confirming the Diagnosis of LD

The Centers for Disease Control (CDC) case definition for confirming the diagnosis of LD can be summarized as physician-diagnosed EM of more than 5 cm diameter, or any late manifestations of the disease—neurological, cardiac, arthritis, etc.—associated with a positive Lyme serology. It is important to note that this CDC definition is tailored for epidemiologic surveillance purposes and should not dictate management for any individual patient.88

History and Physical Examination. Emergency physicians—especially those practicing in the northeastern United States—must maintain a high index of suspicion for LD between May and October. In many cases, the diagnosis of LD is no more complicated than taking a history and performing a detailed physical exam that reveals characteristic EM or other signs of early disseminated LD. In this regard, asking a patient, "Have you been bitten by any ticks?" is not sufficient, and can be misleading, since most patients who eventually develop LD simply do not recall being bitten by a tick. Instead, the inquiry should be directed toward uncovering the possibility that the individual has been the victim of a tick bite.

A fruitful line of questioning would entail asking the patient with a rash where he or she has been during the month prior to presentation. Remember, a patient with 7-NP who lives in Arizona, where the prevalence of LD is low, may have been vacationing in Rhode Island, which is endemic for the disease. In addition, patients should be asked about specific recreational activities—gardening, hiking, camping or fishing—that might have placed them at higher risk for being bitten by a tick. Furthermore, the season of onset for these early syndromes can be suggestive. However, patients can present with TBD in all months and, in fact, the mortality rate is higher in patients with RMSF who present "out of season."86 Finally, while affirmative responses to these questions point toward TBD, negative responses do not rule out tick-mediated pathology.

In the appropriate geographical setting and within the targeted temporal window, the presence of classic EM is diagnostic of LD and no additional testing is indicated. However, because EM can be associated with atypical presentations, the emergency physician must become familiar with these clinical variants. Another example in which diagnostic testing may not be necessary is the presence of lymphocytic meningitis in combination with facial nerve palsy in the characteristic setting. This combination overwhelmingly suggests LD. In most other cases, laboratory testing for antibodies to borrelial proteins will be required to corroborate the diagnosis.

Serological Testing. To confirm the diagnosis of LD, the CDC currently recommends a two-step procedure similar to that used for HIV testing (i.e., a screening ELISA followed by a confirmatory Western blot in positive or borderline ELISA).89 This approach is supported by recent studies that suggest that a standardized ELISA test followed up by Western blot for all positive or borderline tests yields fairly specific results.90 As with most tests in medicine, higher specificity generally comes at the price of lower sensitivity.91 Despite widespread use of these serological methods, there is no universally agreed upon standard for what constitutes a positive Western blot.92-94

Current testing, while vastly improved, is still imperfect, and misinterpretation of either false-negative and false-positive results can have serious clinical consequences. Therefore, ED physicians who order these tests must understand their intrinsic limitations. Measurable host antibodies to borrelial proteins frequently take several weeks to develop.36-95 Early seronegativity does not exclude the diagnosis of LD.

False-positive tests by ELISA occur with many different infectious conditions, including Epstein-Barr viral infection, varicella, endocarditis, ehrlichiosis, gingivitis from non-pathogenic spirochetes normally present in the mouth, other spirochetal infections, immunologic conditions (systemic lupus erythematosus [SLE], rheumatoid arthritis [RA]), and malignancies.95,96-99 Another potential source of error is encountered in the patient who has a previous history of LD. In this regard, it should be emphasized that antibodies can persist for many years.92-94,100 Finally, routine lab tests such as CBC and ESR are generally normal, although 40% of patients will have one or more abnormalities on liver function testing.64,100

In the ED setting, treatment decisions will be based upon clinical and epidemiologic parameters. While early treatment may cause later seronegativity, most patients with culture-proven EM will seroconvert even with treatment.18,36,95,101 Specific diagnostic tests (culture and PCR) are not routinely available to the emergency physician.

Management Guidelines and Disposition

Asymptomatic Tick Bites. In most cases, no treatment is recommended in patients who present with an asymptomatic tick bite. However, if after considering all the relevant historical and epidemiological factors, the ED physician, in collaboration with the patient, decides that antimicrobial treatment is the most prudent clinical approach, the following recommendations can be made. A 10-day course of amoxicillin (250-500 mg po tid) for children and 10-day course of doxycycline (100 mg po bid) in adults is appropriate. (See Table 2.)

Tick Removal. Removal of ticks is best accomplished by grasping the tick as close as possible to the skin with very fine tweezers and pulling slowly, but firmly, and perpendicularly away from the skin.102 Retained tick parts may predispose to secondary bacterial infection but will not increase the risk of LD.103 Some physicians advocate injecting a small wheal of lidocaine with epinephrine using a fine-gauge needle directly beneath the tick.104

Gloves should be worn and the skin should be thoroughly disinfected after tick removal. The tick’s body should not be squeezed, since there is a theoretical possibility that this might "inject" infectious material into the patient’s skin. It should be re-emphasized that most manifestations of LD will go away without treatment with antibiotics, but treatment will shorten the duration of symptoms and prevent development of subsequent manifestations.

Conclusive data regarding the effect of LD on the fetus in pregnant women are lacking.105,106 In general, however, the threshold for treating pregnant patients and for using parenteral medications should be lower. Tetracyclines are contraindicated in pregnant women and in children less than 9 years of age. (See Table 2.)

Solitary Erythema Migrans. Solitary EM requires antibiotic therapy—the only question being the choice and duration. Oral doxycycline or amoxicillin are considered by most experts to be the drugs of choice.18,107 Alternatives include phenoxymethyl penicillin, tetracycline, and cefuroxime, the only drug approved by the FDA for this use.18 Erythromycin and azithromycin have been used as alternatives but a recent study comparing amoxicillin and azithromycin, showed amoxicillin to be superior.108 Varying durations of therapy have been recommended in the literature, ranging between 10 and 30 days.18 Most physicians recommend 14-21 days of therapy. 107 A three-week course seems prudent, until controlled trials dictate otherwise. Patients with systemic symptoms and those with a longer duration of disease should be treated with four weeks of therapy.

Summer Flu Syndrome. When the geographical and historical circumstances so dictate, the "summer flu" syndrome can probably be treated as EM. Doxycycline has the advantage of activity against RMSF and ehrlichiosis.

Early Disseminated Disease. Early disseminated disease is usually treated with parenteral antibiotics.107 Patients in whom parenteral therapy is mandatory include those with meningitis, radiculoneuritis, and high-degree heart block. Some physicians treat isolated 7-NP with oral antibiotics, but for a longer duration (21-30 days).107 Some experts advocate doing a spinal tap on all patients with Lyme-associated 7-NP. Their reasoning is that those with pleocytosis require parenteral therapy, whereas those without cells can be treated orally. As is the case for many treatment decisions regarding LD syndromes, there are insufficient scientific data to resolve this issue.

Meningitis and radiculoneuritis are treated intravenously for 2-3 weeks. Ceftriaxone has excellent activity against B. burgdoferi and has the pharmacologic advantage of a long half-life. Intravenous penicillin G can also be used.18 Symptoms usually resolve over days although resolution of motor signs and symptoms can take longer. Treatment of chronic LD syndromes is outside the purview of the emergency physician.


Preventing TBD requires implementation of specific environmental, personal, and vaccine-related strategies. Proven environmental techniques include insecticide application and wildlife management, (i.e., fencing to exclude deer from a given area).3

Personal measures, including the use of insect repellants and prompt tick removal, can also be helpful. Wearing light-colored clothing to make ticks more visible, long pants and sleeves, and tucking pant legs into the socks are all recommended, although difficult to comply with in hot summer weather. Staying to the center of trails when hiking may reduce tick exposure. Daily tick inspections with removal of any that are found may help to identify ticks before they can transmit disease. Finally, application of permethrin to clothing and DEET to skin are effective tick repellants. Caution is necessary in children, who can develop neurotoxicity from DEET if used in high concentrations.

Phase 3 human vaccine trials are currently ongoing in endemic areas. Phase 1 and 2 trials of a vaccine to Osp A, a borrelial surface protein, were shown to be safe and immunogenic. Vaccine is presently available on a protocol basis only.


Patients with TBD frequently present to the ED with signs and symptoms that can be confused with many common disorders, including allergic conditions, viral infections, and non-specific "summer flu" syndromes. Because LD can progress from a benign condition to a serious, disseminated condition with serious neurological, cardiac, and rheumatological sequelae, the emergency physician must maintain a high index of suspicion for tick-related conditions and be familiar with indications for treatment, especially in the appropriate epidemiologic setting.


1. Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis: An epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 1977;20:7-17.

2. Barbour AG, Fish D. The biological and social phenomenon of Lyme disease. Science 1993;260:1610-1616.

3. Fish D. Environmental risk and prevention of Lyme disease. Am J Med 1995;98:2S-8S; discussion 8S-9S.

4. Lyme Disease—United States, 1991-1992. MMWR Morb Mortal Wkly Rep 1993;42:345-348.

5. Lyme Disease—United States, 1994. MMWR Morb Mortal Wkly Rep 1995;44:459-462.

6. Lyme Disease—United States, 1995. MMWR Morb Mortal Wkly Rep 1996;45:481-484.

7. Coyle BS, Strickland, GT, Liang, YL. The public health impact of Lyme disease in Maryland. J Infect Dis 1996;173:1260-1262.

8. Falco RC, Fish D. Prevalence of Ixodes dammini near the homes of Lyme disease patients in Westchester County, New York. Am J Epidemiol 1988;127:826-830.

9. Maupin GO, Fish D, Zultowsky J, et al. Landscape ecology of Lyme disease in a residential area of Westchester County, New York. Am J Epidemiol 1991;133:1105-1113.

10. Salgo MP, Telzak EE, Currie B, et al. A focus of Rocky Mountain spotted fever within New York City. N Engl J Med 1988;318:1345-1348.

11. Costello CM, Steere AC, Pinkerton RE, et al. A prospective study of tick bites in an endemic area for Lyme disease. J Infect Dis 1989;159:136-139.

12. Shapiro ED, Gerber MA, Holabird NB, et al. A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites [see comments]. N Engl J Med 1992;327:1769-1773.

13. Strle F, Cheng Y, Cimperman J, et al. Persistence of Borrelia burgdorferi sensu lato in resolved erythema migrans lesions. Clin Infect Dis 1995;21:380-389.

14. Asbrink E, Hovmark A. Successful cultivation of spirochetes from skin lesions of patients with erythema chronica migrans afzelius and acrodermatitis chronica atrophicans. Acta Pathol Microbiol Immunol Scand 1985;93:161-163.

15. Goodman JL, Bradley JF, Ross AE, et al. Bloodstream invasion in early Lyme disease: Results from a prospective, controlled, blinded study using the polymerase chain reaction. Am J Med 1995;99:6-12.

16. Luft BJ, Steinman CR, Neimark HC, et al. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. [Published erratum appears in JAMA 1992;268:872.] [see comments]. JAMA 1992;267:1364-1367.

17. Nadelman RB, Pavia CS, Magnarelli LA, et al. Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease. Am J Med 1990;88:21-26.

18. Nocton JJ, Steere AC. Lyme disease. Adv Intern Med 1995;40:69-117.

19. Piesman J, Mather TN, Sinsky RJ, et al. Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol 1987;25:557-558.

20. Piesman J, Maupin GO, Campos EG, et al. Duration of adult female Ixodes dammini attachment and transmission of Borrelia burgdorferi, with description of a needle aspiration isolation method. J Infect Dis 1991;163:895-897.

21. Piesman J. Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. J Infect Dis 1993;167:1082-1085.

22. Ribiero J. Role of saliva in blood-feeding by arthropods. Ann Rev Entomol 1987;32:463-478.

23. Zung JL, Lewengrub S, Rudzinska MA, et al. Fine structural evidence for the penetration of the Lyme disease spirochete, Borrelia burgdorferi through the gut and salivary tissues of Ixodes dammini. Can J Zoo. 1989;67:1737-1748.

24. Benach JL, Coleman JL, Skinner RA, et al. Adult Ixodes dammini on rabbits: a hypothesis for the development and transmission of Borrelia burgdorferi. J Infect Dis 1987;155:1300-1306.

25. Strle F, Nelson J, Ruzic-Sabljic E, et al. European Lyme borreliosis: 231 culture-confirmed cases involving patients with erythema migrans. Clin Infect Dis 1996;23:61-65.

26. Patmas MA, Remorca C. Disseminated Lyme disease after short-duration tick bite. J Spirochet Tick-Borne Dis 1994;1:77-78.

27. Malane MS, Grant-Kels JM, Feder HM, et al. Diagnosis of Lyme disease based on dermatologic manifestations. Ann Intern Med 1991;114:490-498.

28. Bosler EM, Ormiston BG, Coleman JL, et al. Prevalence of the Lyme disease spirochete in populations of white-tailed deer and white-footed mice. Yale J Biol Med 1984;57:651-659.

29. 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 1996;100:502-508.

30. Melski JW, Reed KD, Mitchell PD, et al. Primary and secondary erythema migrans in Central Wisconsin. Arch Dermatol 1993;129:709-716.

31. Berger BW. Dermatologic manifestations of Lyme disease. Rev Infect Dis 1989;11:S1475-S1481.

32. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med 1995;98:15S-23S; discussion 23S-24S.

33. Feder HM, Jr., Hunt MS. Pitfalls in the diagnosis and treatment of Lyme disease in children. JAMA 1995;274:66-68.

34. Feder HM, Jr., Whitaker DL. Misdiagnosis of erythema migrans. Am J Med 1995;99:412-419.

35. Mitchell PD, Reed KD, Vandermause MF, et al. Isolation of Borrelia burgforferi from skin biopsy specimens of patients with erythma migrans. Clin Microbiol Infect Dis 1992;99:104-107.

36. Aguero-Rosenfeld ME, Nowakowski J, Bittker S, et al. Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans. J Clin Microbiol 1996;34:1-9.

37. Feder HM, Jr., Gerber MA, Krause PJ. Early Lyme disease: A flu-like illness without erythema migrans. Pediatrics 1993;91:456-459.

38. Coyle PK. Neurologic complications of Lyme disease. Rheum Dis Clin North Am 1993;19:993-1009.

39. Garcia-Monco JC, Benach JL. Lyme neuroborreliosis. Ann Neurol 1995;37:691-702.

40. Belman AL, Iyer M, Coyle PK, et al. Neurologic manifestations in children with North American Lyme disease. Neurology 1993;43:2609-2614.

41. Reik L, Jr., Burgdorfer W, Donaldson JO. Neurologic abnormalities in Lyme disease without erythema chronicum migrans. Am J Med 1986;81:73-78.

42. Pachner AR. Early disseminated Lyme disease: Lyme meningitis. Am J Med 1995;98:30S-37S; discussion 37S-43S.

43. Elmore JG, Horwitz RI, Quagliarello VJ. Acute meningitis with a negative Gram’s stain: Clinical and management outcomes in 171 episodes. Am J Med 1996;100:78-84.

44. Clarke JR, Carlson RD, Pachner AR, et al. Facial paralysis in Lyme disease. Laryngoscope 1985;95:1341-1345.

45. Christen H, Bartlau N, Hanefield F, et al. Peripheral facial palsy in childhood: Lyme borreliosis to be suspected unless proven otherwise. Acta Pediatr Scand 1990;79:1219-1224.

46. Markby DP. Lyme disease facial palsy: Differentiation from Bell’s palsy. [See comments]. BMJ 1989;299:605-606.

47. Halperin JJ, Golightly M. Lyme borreliosis in Bell’s palsy. Long Island Neuroborreliosis Collaborative Study Group. [see comments]. Neurology 1992;42:1268-1270.

48. Olsson I, Engervall KA, Hovmark A. Tick-borne borreliosis and facial palsy. Acta Otolaryngol (Stockholm) 1988;105:100-107.

49. Roberg M, Ernerudh J, Forsberg P, et al. Acute peripheral facial palsy: CSF findings and etiology. Acta Neurol Scand 1991;83:55-60.

50. Puhakka HJ, Laurikainen E, Viljanen M, et al. Peripheral facial palsy caused by Borrelia burgdorferi and viruses in south-western Finland. Acta Otolaryngol [supplement] 1992;492:103-106.

51. Kuiper H, Devriese PP, de Jongh BM, et al. Absence of Lyme borreliosis among patients with presumed Bell’s palsy. Arch Neurol 1992;49:940-943.

52. Halperin JJ. Neuroborreliosis. Am J Med 1995;98:4A-52S-59S.

53. Sigal LH. Early disseminated Lyme disease: Cardiac manifestations. Am J Med 1995;98:25S-28S; discussion 28S-29S.

54. Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: Cardiac abnormalities of Lyme disease. Ann Intern Med 1980;93:8-16.

55. van der Linde MR. Lyme carditis: Clinical characteristics of 105 cases. Scand J Infect Dis [supplement] 1991;77:81-84.

56. Horowitz HW, Belkin RN. Acute myopericarditis resulting from Lyme disease. Am Heart J 1995;130:176-178.

57. Bruyn GA, De Koning J, Reijsoo FJ, et al. Lyme pericarditis leading to tamponade. Br J Rheumatol 1994;33:862-866.

58. Lesser RL. Ocular manifestations of Lyme disease. Am J Med 1995;98:60S-62S.

59. Karma A, Seppala I, Mikkila H, et al. Diagnosis and clinical characteristics of ocular Lyme borreliosis. Am J Ophthalmol 1995;119:127-135.

60. Aaberg TM. The expanding ophthalmologic spectrum of Lyme disease. Am J Ophthalmol 1989;107:77-80.

61. Steere AC, Duray PH, Kauffmann DJH, et al. Unilateral blindness caused by infection with the Lyme disease spirochete, Borrelia burgdorferi. Ann Intern Med 1985;103:382-384.

62. Preac-Mursic V, Pfister HW, Spiegel H, et al. First isolation of Borrelia burgdorferi from an iris biopsy. J Clin Neuroophthalmol 1993;13:155-161; discussion 162.

63. Steere AC. Musculoskeletal manifestations of Lyme disease. Am J Med 1995;98:44S-48S; discussion 48S-51S.

64. Horowitz HW, Dworkin B, Forseter G, et al. Liver function in early Lyme disease. Hepatology 1996;23:1412-1417.

65. Steere AC, Malawista SE, Hardin JA, et al. Erythema chronicum migrans and Lyme arthritis: The enlarging clinical spectrum. Ann Intern Med 1977;86:685-698.

66. Ilowite NT. Muscle, reticuloendothelial, and late skin manifestations of Lyme disease. Am J Med 1995;98:63S-68S.

67. Dumler JS, Bakken JS. Ehrlichial diseases of humans: Emerging tick-borne infections. Clin Infect Dis 1995;20:1102-1110.

68. Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med 1994;120:736-743.

69. Walker DH. Human ehrlichiosis: More trouble from ticks. Hosp Pract 1996;31:47-57.

70. Ratnasamy N, Everett ED, Roland WE, et al. Central nervous system manifestations of human ehrlichiosis. Clin Infect Dis 1996;23:314-319.

71. Wong S, Grady LJ. Ehrlichia infection as a cause of severe respiratory distress (letter). N Engl J Med 1996;334:273.

72. Vugia DJ, Holmberg E, Steffe EM, et al. A human case of monocytic ehrlichiosis with adult respiratory distress syndrome in northern California. West J Med 1996;164:525-528.

73. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996;275:199-205.

74. Krause PJ, Telford SR, Pollack RJ, et al. Babesiosis: An underdiagnosed disease of children. Pediatrics 1992;89:1045-1048.

75. Boustani M, Gelfand J. Babesiosis. Clin Infect Dis 1996;22:611-615.

76. Meldrum SC, Birkhead GS, White DJ, et al. Human babesiosis in New York State: An epidemiological description of 136 cases. Clin Infect Dis 1992;15:1019-1023.

77. Mitchell PD, Reed KD, Hofkes JM. Immunoserologic evidence of coinfection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrhichia species in residents of Wisconsin and Minnesota. J Clin Microbiol 1996;34:724-727.

78. Paparone PW, Glenn WB. Lyme disease with concurrent ehrlichiosis. J Am Osteopath Assoc 1994;94:568-570, 573, 577.

79. Benach JL, Coleman JL, Habicht GS, et al. Serological evidence for simultaneous occurrences of Lyme disease and babesiosis. J Infect Dis 1985;152:473-477.

80. Grunwaldt E, Barbour AG, Benach JL. Simultaneous occurrence of babesiosis and Lyme disease [letter]. N Engl J Med 1983;308:1166.

81. Krause P, Telford S, Spielman A, et al. Concurrent Lyme disease and babesiosis—evidence for increased severity and duration of illness. JAMA 1996;275:1657-1660.

82. Marcus LC, Steere AC, Duray PH, et al. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis: Demonstration of spirochetes in the myocardium. Ann Intern Med 1985;103:374-376.

83. Westerman EL. Rocky Mountain spotless fever: A dilemma for the clinician. Arch Intern Med 1982;142:1106-1107.

84. Weber DJ, Walker DH. Rocky Mountain spotted fever. Infect Dis Clin North Am 1991;5:19-35.

85. Helmick CG, Bernard KW, D’Angelo LJ. Rocky Mountain spotted fever: Clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis 1984;150:480-488.

86. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis 1995;20:1118-1121.

87. Woodward TE. Rocky Mountain spotted fever: Epidemiological and early clinical signs are keys to treatment and reduced mortality. J Infect Dis 1984;150:465-468.

88. Case definitions for public health surveillance. MMWR Morb Mortal Wkly Rep 1990;39:19-21.

89. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995;44:590-591.

90. Johnson BJ, Robbins KE, Bailey RE, et al. Serodiagnosis of Lyme disease: Accuracy of a two-step approach using a flagella-based ELISA and immunoblotting. J Infect Dis 1996;174:346-353.

91. LeWitt MH. Biostatistics for the clinical physician. Hosp Phys 1996:41-44.

92. Dressler F, Whalen JA, Reinhardt BN, et al. Western blotting in the serodiagnosis of Lyme disease [see comments]. J Infect Dis 1993;167:392-400.

93. Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol 1995;33:419-427.

94. Zoller L, Burkard S, Schafer H. Validity of western immunoblot band patterns in the serodiagnosis of Lyme borreliosis. J Clin Microbiol 1991;29:174-182.

95. Magnarelli LA. Current status of laboratory diagnosis for Lyme disease. Am J Med 1995;98:10S-12S; discussion 12S-14S.

96. Feder HM, Jr., Gerber MA, Luger SW, et al. False-positive serologic tests for Lyme disease after varicella infection [letter]. N Engl J Med 1991;325:1886-1887.

97. Kaell AT, Volkman DJ, Gorevic PD, et al. Positive Lyme serology in subacute bacterial endocarditis: A study of four patients. JAMA 1990;264:2916-2918.

98. Magnarelli LA, Miller JN, Anderson JF, et al. Cross-reactivity of nonspecific treponemal antibody in serologic tests for Lyme disease. J Clin Microbiol 1990;28:1276-1279.

99. Magnarelli LA, Anderson JF, Johnson RC. Cross-reactivity in serological tests for Lyme disease and other spirochetal infections. J Infect Dis 1987;156:183-188.

101. Dattwyler RJ, Volkman DJ, Luft BJ, et al. Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. [see comments] N Engl J Med 1988;319:1441-1446.

100. Feder HM, Jr., Gerber MA, Luger SW, et al. Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease. Clin Infect Dis 1992;15:788-793.

102. Needham GR. Evaluation of five popular methods of tick removal. Pediatrics 1985;75:997-1002.

103. Rossignol P, Feinsod FM. Arthropods directly causing human injury. In: Warren KS, Mahmoud AAF, eds. Tropical and Geographic Medicine. 2nd ed. New York: McGraw-Hill Information Sevices Company; 1990:519-532.

104. Murakami E. Lyme disease case in the Lower Mainland and a new wood-tick removal technique. In: Ziska M, ed. VIIIth Annual LDF International Scientific Conference on Lyme Borreliosis and Other Spirochetal and Tick-borne Diseases. Vancouver, Canada; 1995.

105. MacDonald AB. Gestational Lyme borreliosis. Rheumatic diseases. Clin North Am 1989;15:657-677.

106. Markowitz LE, Steere AC, Benach JL, et al. Lyme disease during pregnancy. JAMA 1986;255:3394-3396.

107. Rahn DW, Malawista SE. Lyme disease: Recommendations for diagnosis and treatment [see comments]. Ann Intern Med 1991;114:472-481.

108. Luft BJ, Dattwyler RJ, Johnson RC, et al. Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial. Ann Intern Med 1996;124:785-791.

Physician CME Questions

81. The most common tick vector of Lyme disease in the eastern United States, Ixodes scapularis:

A. is only found in the New England states.

B. has a bite that is noticed by nearly all patients diagnosed with Lyme disease.

C. can transmit babesiosis and ehrlichiosis as well.

D. requires 72 hours of attachment to the host to transmit disease.

82. Ehrlichiosis is another tick-borne disease that:

A. can present with non-specific findings such as fevers, chills, myalgias, and arthralgias.

B. is generally associated with a high WBC count and hyperamylasemia.

C. is an intra-erythrocytic parasite similar to malaria.

D. should be treated only after serologic confirmation or a positive PCR test of blood.

83. Regarding the pathophysiology of Lyme disease, all the following statements are true except :

A. following the bite of a tick infected with B. burgdorferi, substances in tick saliva help the organism establish infection in the skin.

B. the spirochete immediately invades host blood vessels and travels to the CNS within the first two days of infection.

C. B. burgdorferi has a tropism for skin, CNS, cardiac, and articular tissues.

D. some tick bites are responsible for transmitting multiple infecting organisms.

84. Well-described manifestations of Lyme disease include:

A. 7th cranial nerve palsy.

B. lymphocytic meningitis.

C. an acral petechial rash that spreads centripetally.

D. varying degrees of cardiac conduction disturbances.

85. The diagnosis of Lyme disease:

A. always requires a positive serology for confirmation.

B. is most reliably made by seeing EM in an epidemiologically appropriate setting.

C. always requires Western blot confirmation of a positive ELISA test.

D. requires the patient to have traveled to one of the eight endemic states.

86. Possible treatment of a patient with EM and 7th nerve palsy might include all the following regimens except:

A. one month of doxycycline.

B. one month of amoxicillin.

C. IV ceftriaxone if the patient had pleocytosis in the CSF.

D. IV clindamycin and ciprofloxcacin.

87. All of the following are true of erythema migrans (EM) except:

A. classic EM is a flat red rash with central clearing found 7-10 days after the bite of an infected Ixodes tick.

B. only about a third of early Lyme disease patients have EM.

C. a typical EM rash may appear uniform in color, centrally darkened, vesicular, or necrotic.

D. untreated, EM will disappear on its own in several weeks.

88. Regarding serologic testing for Lyme disease, which of the following statements is false?

A. ELISA tests may be falsely positive in patients with certain viral infections, other spirochetal infections, and patients with malignancies and immunologic disorders.

B. In early Lyme disease, serologic testing may be falsely negative because it can take several weeks for the host to mount an antibody response to B. burgdorferi.

C. Western blot testing should be done to confirm positive ELISA tests.

D. All patients with a positive ELISA test should be treated for Lyme disease.