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Journal of the American Academy of Physician Assistants:
doi: 10.1097/01.JAA.0000436285.57691.8c
Infectious Diseases

Diagnosing and managing Lyme disease

Ziegler, Rachel M.; Didas, Colleen M. MPH, MMS, PA-C; Smith, Jami S. MPA, MEd, PA-C

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Continued Medical Education
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Author Information

Rachel M. Ziegler is a master of public health and physician assistant student at Arcadia University in Glenside, Pennsylvania. Colleen M. Didas is a recent graduate of the Arcadia University PA program with a dual degree in public health. Jami S. Smith works at Drexel University College of Medicine in Philadelphia, Pennsylvania, and practices emergency medicine in the Philadelphia area. The authors have indicated no relationships to disclose relating to the content of this article.

Earn Category I CME Credit by reading this article and the article beginning on page 27 and successfully completing the posttest on page 32. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of November 2013.

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Abstract

ABSTRACT: All primary care providers should be familiar with the symptoms, diagnostic criteria, and treatments for Lyme disease. This tick-borne illness is increasing in incidence and geographic spread in the United States.

Lyme disease is the most common vector-borne illness in the United States.1 Because the disease affects multiple systems, patients may present with dermatologic, neurologic, rheumatologic, and/or cardiac symptoms. According to the CDC, the incidence of Lyme disease increased 9.7% from 2010 to 2011, with 33,097 cases reported in 2011.2 The nationwide economic effect of Lyme disease was estimated at $203 million in combined medical and nonmedical spending for 2002.3 Cases of Lyme disease typically have been concentrated in the northeast and north-central United States; however, over the past decade as incidence has increased, these endemic areas have expanded.4

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Analysis of data from 1992 to 2006 found that the incidence of Lyme disease was highest among children aged 5 to 14 years and that 53% of cases were reported in young males.1 In its early stages, Lyme disease can be managed by primary care practitioners, who should be familiar with the symptoms, diagnostic criteria, and treatment regimens. Promptly recognizing the signs and symptoms and instituting proper treatment of Lyme disease may reduce the severity or chronicity of symptoms for patients.

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CAUSES

Borrelia burgdorferi, a bacterial spirochete, is the causative agent of Lyme disease. B. burgdorferi occurs naturally in small vertebrates, such as mice or squirrels, which act as reservoir hosts for the bacteria. Ixodes scapularis and Ixodes pacificus (commonly known as deer ticks or blacklegged ticks) feed on the blood of reservoir hosts and become infected with B. burgdorferi.5 Ticks then transmit the bacteria to other reservoir hosts, or incidental hosts such as humans, during subsequent blood meals.1 The tick needs to be attached between 24 and 48 hours to transmit the bacterium to the new host.6 See Figure 1 for an example of an engorged tick after a feeding. Ticks in the nymphal stage, which occurs from June through August, are most likely to transmit the infection. Accordingly, most cases of erythema migrans, the skin rash characteristic of Lyme disease, occur during the summer months.7

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SIGNS AND SYMPTOMS

Consider Lyme disease in patients who exhibit symptoms consistent with the disease, live in endemic areas, and have risk factors for tick exposure. Lyme disease is divided into three stages: early localized, early disseminated, and late disseminated.

Early localized disease occurs 3 to 30 days after tick exposure and typically is characterized by erythema migrans (Figure 2), which originates at the site of the tick bite.6 Erythema migrans lesions typically begin as a red macule or papule and expand over the course of days to weeks to form a large annular, erythematous lesion with varying degrees of central clearing.7 Lesions typically are asymptomatic and can range in diameter from 5 to 70 cm.7 Other systemic symptoms of early localized infection include fever, fatigue, arthralgias, and myalgias.6

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Figure 2
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Early disseminated disease occurs once B. burgdorferi enters the bloodstream and is deposited in distant sites within the body. This can occur days to weeks after the initial appearance of an erythema migrans lesion.8 Early disseminated disease most commonly manifests as multiple erythema migrans lesions. Other characteristic manifestations of early disseminated disease include Lyme neuroborreliosis, Lyme carditis, fever, myalgias, arthralgias, headache, and/or fatigue.8 Neurologic manifestations of Lyme neuroborreliosis include meningitis, facial palsy, headache, meningismus, numbness, and tingling.8 Lyme carditis typically presents as atrioventricular nodal dysfunction with symptoms of light-headedness, syncope, dyspnea, palpitations, and/or chest pain.10 First-, second-, and third-degree atrioventricular (AV) heart block have been documented with Lyme carditis.10 Figure 3 shows second-degree AV block from Lyme carditis. Additional clinical findings of Lyme carditis may include pericarditis, endocarditis, myocarditis, pericardial effusion, myocardial infarction, coronary artery aneurysm, QT-interval prolongation, tachyarrhythmias, and heart failure.10

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Late disseminated disease occurs weeks to months after the initial infection and manifests as rheumatologic and/or neurologic symptoms.8 Monoarticular and oligoarticular arthritis can be intermittent or chronic, and the knees are the most commonly affected joints.6 Neurologic manifestations of late disseminated disease can include encephalitis, encephalopathy, and polyneuropathy.8

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DIFFERENTIAL DIAGNOSIS

Table 1 describes the stages of Lyme disease, symptoms, and possible conditions to consider in the differential diagnosis. Lyme disease must also be differentiated from southern tick-associated rash illness (STARI), another tick-transmitted disease that manifests as a rash and can be accompanied by fatigue, headache, myalgias, and arthralgias.6 STARI was initially reported in the southern United States, but cases have since been reported in the Midwest and Northeast.6 Distinguishing Lyme disease from STARI is difficult without identifying the tick.

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COINFECTIONS

Deer ticks may be concomitantly infected with B. burgdorferi, Anaplasma phagocytophilum, and Babesia microti in endemic areas, so patients may also be coinfected.6 Consider coinfection in patients who present with initial symptoms that are more severe than typically observed in patients with Lyme disease alone. For example, suspect coinfection in patients with unexplained leukopenia, thrombocytopenia, or anemia; patients with a high-grade fever that lasts 48 hours despite appropriate antibiotic treatment for Lyme disease; and patients whose erythema migrans rash has resolved with appropriate antibiotic treatment, but who experience persistent or worsening viral infection-like symptoms. In these patients, serologic testing is recommended to detect coinfection.11 Blood parasite smears, serologic testing, and/or polymerase chain reaction (PCR) are routinely done in areas where coinfection rates with A. phagocytophilum or B. microti are high.6

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DIAGNOSIS

Diagnosis of Lyme disease varies depending on the patient's stage of disease at presentation. Because the tick must be attached for 24 to 72 hours to transmit the B. burgdorferi bacteria, removing the tick within 24 hours of attachment is usually sufficient to prevent Lyme disease.12 Although tick infection is often dependent on the region and prevalence of infected ticks, patients have less than a 5% risk of acquiring Lyme disease from a single tick bite.13

Lyme disease can be detected through serologic testing; however, testing is not advised in certain situations. For example, serologic tests are not advised for patients presenting with erythema migrans, especially those living in endemic areas with potential tick exposure. The presence of erythema migrans merits the diagnosis of Lyme disease and commencement of antibiotic therapy.12

Because of the high incidence of false-positives, serologic testing also is not advised for patients presenting with nonspecific symptoms and no history of tick exposure in Lyme-endemic areas.6

The standard serologic testing procedure, as recommended by the CDC, involves a two-test approach in order to accurately identify active disease and previous infection. Specimens that are negative by a sensitive enzyme immunoassay (EIA) or immunofluorescent assay (IFA) do not require further testing. Specimens that are positive by a sensitive EIA or IFA should be tested via Western immunoblot as the second step of the diagnosis process.14 When Western immunoblot is used during the first 4 weeks of disease onset (early Lyme disease), both IgM and IgG procedures should be performed.14 A positive IgM test result by itself is not recommended for use in determining active disease in patients who have been ill for longer than 1 month due to the high likelihood of a false-positive test for a current infection.14

When antibodies are not detectable or not diagnostic in the acute-phase serum specimen, a convalescent-phase specimen should be collected 2 to 4 weeks later and tested for B. burgdorferi antibodies.15 Patients with late-stage Lyme disease typically have elevated IgG antibody levels in response to B. burgdorferi antigens.14 IgM and IgG B. burgdorferi antibodies may persist for many years after successful treatment of Lyme disease; thus, persistent seropositivity is not necessarily an indication of treatment failure.15

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TREATMENT AND PROGNOSIS

The Infectious Diseases Society of America (IDSA) published national treatment guidelines for Lyme disease in 2000 and revised the guidelines in 2006. According to these guidelines, a single prophylactic 200 mg oral dose of doxycycline may be offered to adults and children 8 years and older (4 mg/kg up to a maximum dose of 200 mg) when all of the following criteria are met:

* the attached tick can be reliably identified as an adult or nymphal stage deer tick that is estimated to have been attached for more than 36 hours, based on the degree of tick engorgement or certainty regarding the time 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 20% or more

* doxycycline treatment is not contraindicated.11

According to IDSA guidelines, if these criteria are not met, prophylactic treatment should not be provided because of the adverse effects of antibiotics, associated costs, and low likelihood of infection. In one IDSA trial, the number-needed-to-treat with doxycycline to prevent one case of Lyme disease was 40.13 In the event that doxycycline is contraindicated, IDSA guidelines also do not advise prophylactic administration of amoxicillin because of a lack of effectiveness data of short-course therapy.11 See Table 2 for a breakdown of the stages of Lyme disease, manifestations, and treatment options.

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Doxycycline is not recommended in pregnant women and children under age 8 years. Identifying and treating Lyme disease during pregnancy is especially important as significant associations have been found between untreated Lyme disease and adverse pregnancy outcomes, including spontaneous abortion, stillbirth, and preterm births.16 Pregnant and lactating patients may be treated similarly to non-pregnant patients with the same disease manifestations, except that doxycycline should be avoided (Table 2).11

The prognosis of Lyme disease is most favorable when treated early in the disease course with the appropriate antibiotic for the recommended amount of time. Early localized and early disseminated Lyme disease is effectively eradicated in 90% of individuals when treated with a single course of antibiotics for 14 days. Follow-up studies of patients treated according to IDSA recommendations show that patients' overall health status is comparable to an uninfected control population.13 Oral antibiotic therapy with doxycycline is most often the only therapy needed to treat early localized disease and prevent disease progression.

Short-term residual myalgias and arthralgias typically resolve within a few months after appropriate treatment. The more serious complications of early disseminated Lyme disease, such as heart block or meningitis, also have favorable outcomes with antibiotic use. If complications are severe, initiate parenteral therapy and transition to oral therapy with clinical improvement.

Manifestations of late disseminated Lyme disease, such as arthritis, may be difficult to eradicate and a single 28-day course of antibiotics is not always successful. In this event, some patients may warrant a second, 4-week course of either antibiotic therapy. These symptoms then generally resolve with overall positive health outcomes.13 Adult patients with arthritis who also have neurologic disease require more intensive therapy, such as with parenteral antibiotic therapy.

Although most patients with Lyme disease respond well to appropriate therapy with few lingering manifestations or effects on daily life, a small portion of patients report long-standing complaints. These frequently include symptoms of residual musculoskeletal pain and difficulties with concentration or short-term memory, and may warrant consultation with a specialist. These post-Lyme disease symptoms usually are mild, self-limiting, and do not require treatment. Symptoms that last longer than 6 months are called post-Lyme disease syndrome (PLDS).17

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LATER SEQUELAE OF LYME DISEASE

Studies demonstrate that a small number of patients who received recommended Lyme disease treatment still report multiple, nonspecific symptoms persisting for months to years. This persistence of symptoms has been called both PLDS and chronic Lyme disease, and is a topic of debate in the scientific community because some healthcare providers do not recognize the existence of this diagnosis. However, the IDSA, which dictates the diagnostic and treatment guidelines for Lyme disease, includes a proposed definition and treatment guidelines for PLDS, so it is recognized as a valid diagnosis.

Symptoms of unresolved Lyme disease (PLDS or chronic Lyme disease) include fatigue, myalgias, arthralgias, memory disturbances, and cognitive impairment. Patients report a spectrum of symptoms that range from mild to so disabling that their quality of life is reduced.13 Patients may either present with self-expressed concerns for PLDS or the practitioner may need to consider a previous diagnosis of Lyme disease as a possible cause of chronic systemic complaints. Current IDSA recommendations for PLDS are to consider and evaluate other potential causes of symptoms, and if none are found, then administer symptomatic therapy.11

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PREVENTION

Lyme disease prevention is focused on reducing human exposure to tick bites in order to reduce the risk of infection. At this time, reducing human exposure is the only reliable method of prevention. Practitioners and the general public should be educated about personal protection measures, the signs and symptoms of infection, and the most appropriate antibiotic therapy. Prevention education and awareness is key to disease management, as current US ecologic conditions (including rising temperatures and reforestation practices) are increasingly favorable to tick-borne infections. Also, the incidence of Lyme disease is steadily increasing, so preventing infection becomes increasingly challenging.12

The most highly emphasized method of prevention is individual exposure prevention. See Table 3 for key elements of patient education on Lyme disease prevention. Other recommendations include landscape management, modifications near residential areas to reduce the habitat and possibility of tick exposure, and applications of acaricide on property or targeted to hosts. Deer population management also has been suggested, but is the least-favored recommendation among the general population.12,18

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Lyme disease locations are spreading geographically and deer ticks are found in rural and suburban areas. The spread of infection is correlated with the spread of deer ticks and the animals they feed on, which are usually located in wooded areas, areas with tall brush or leaves, and in woodpiles. If a person contacts a surface to which a deer tick is attached (for example, grasses or leaves), the tick can transfer to the person. Once on a human, the tick moves on clothing until it encounters an area of least resistance, such as a hairline, waistband elastic, or skin fold, and attaches by burrowing into the skin after a painless bite.6 Thus, protective clothing limits skin exposure and reduces the likelihood of tick bites.

People should perform regular tick checks and promptly remove any ticks found on their bodies.18 The risk of infection is low in the first 24 hours; the transmission of bacterium from the infected tick to the host increases over the time of skin attachment. The recommended method of removing ticks that have started feeding is to use tweezers to grasp the tick at the nearest point of attachment and tug repeatedly. The tugging fatigues the tick's mouth fangs and cleanly releases the tick from the skin. Warn patients against common myths of successful tick removal such as burning the tick with a flame, dousing a tick in solvent, or covering a tick with an occlusive agent.6 These methods are much more harmful to the patient and do not actually remove the tick.

No Lyme disease vaccine is available; LYMErix was removed from the market in 2002 after less than 4 years of availability; the manufacturer cited poor public demand. Although LYMErix was proven effective in Phase III FDA trials and lacked evidence of adverse events reported through the Vaccine Adverse Event Reporting System (VAERS), patients needed booster shots to maintain immunity, and the cost of prevention was higher than the cost of treatment.12,18 Lyme disease prevention relies almost solely on individual behavior and awareness; thus, the emphasis of patient education is critical in reducing disease incidence.

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CONCLUSION

Lyme disease can develop into a serious and chronic disease if not diagnosed and treated promptly. Primary care practitioners should consider Lyme disease in all patients presenting with dermatologic, neurologic, cardiac, or rheumatologic symptoms. Aside from proper diagnosis and management of patients with Lyme disease, education about prevention techniques is clinically important to reducing new or recurrent cases.

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REFERENCES

1. Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease—United States, 1992–2006. MMWR Morb Mortal Wkly Rep. 2008;579.

2. Centers for Disease Control and Prevention. MMWR. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6053a1.htm. Accessed September 24, 2013.

3. Zhang X, Meltzer MI, Peña CA, et al.Economic impact of Lyme disease. Emerg Infect Dis. 2006;12(4):653–660.

4. Centers for Disease Control and Prevention. Interactive Lyme disease map. http://www.cdc.gov/lyme/stats/maps/interactiveMaps.html. Updated September 12, 2012. Accessed January 25, 2013.

5. Bratton RL, Whiteside JW, Hovan MJ, et al.Diagnosis and treatment of Lyme disease. Mayo Clin Proc. 2008;83(5):566–571.

6. Hu LT. In the clinic: Lyme disease. Ann Intern Med. 2012;157(3):ITC2–2-ITC2–16.

7. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet. 2012;379:461–473.

8. Murray TS, Shapiro ED. Lyme disease. Clin Lab Med. 2010;30(1):311–328.

9. Pachner AR, Steiner I. Lyme neuroborreliosis: infection, immunity and inflammation. Lancet Neurol. 2007;6:544–552.

10. Fish AE, Pride YB, Pinto DS. Lyme carditis. Infect Dis Clin N Am. 2008;22:275–288.

11. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. CID. 2006;43:1089–1134.

12. Steere AC, Coburn J, Glickstein L. The emergence of Lyme disease. J Clin Invest. 2004;113(8):1093–1101.

13. Schnarr S, Franz JK, Krause A, Zeidler H. Lyme borreliosis. Best Pract Res Clin Rheumatol. 2006; 20(6):1099–1118.

14. Centers for Disease Control and Prevention. Notice to readers recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 1995;44(31):590–591.

15. Aguero-Rosenfield ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484–509.

16. Lakos A, Solymosi N. Maternal Lyme borreliosis and pregnancy outcome. Int J Infect Diseases. 2010;14:e494–e498.

17. Feder HM Jr, Johnson BJ, O'Connell S, et al. A critical appraisal of “chronic Lyme disease.” New Engl J Med. 2007;357:1422–1430.

18. Shen AK, Mead PS, Beard CB. The Lyme disease vaccine–-a public health perspective. CID. 2008;52:S247–S251.

19. Bhate C, Schwartz R. Lyme disease: part II management and prevention. J Am Acad Dermatol. 2011; 64:639–653.

Keywords:

Lyme disease; deer tick; Borrelia burgdorferi; doxycycline; erythema migrans; neuroborreliosis

© 2013 American Academy of Physician Assistants.

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