Case Based Pediatrics For Medical Students and Residents
Department of Pediatrics, University of Hawaii John A. Burns School of Medicine
Chapter VI.27. Lyme Disease
Judy Makowski Vincent, MD
February 2002

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A 7 year old boy is brought to the pediatric clinic in August with the chief complaint of a large, red circular rash on his left thigh. The rash has been present for 2 weeks and has been enlarging. His father states that 3 weeks ago, the family was visiting relatives at a rural farm in Connecticut, and one day after playing outside in the woods, the boy was found to have a tick attached to his thigh. His father had removed the tick with tweezers; however a red macule remained at the site where the tick had been attached. One week after the tick was removed, a red ring developed around the macule, and then the ring appeared to grow larger by expanding outward, leaving an area of central clearing. The boy has had a mild headache and myalgia, but has been afebrile.

Exam: VS T37.1, P90, RR 20, BP 100/70. He is alert, active, in no distress, and is non-toxic. Over the anterior surface of his left thigh, there is a red ring, 20 cm in diameter, with central clearing, and a central brownish-red macule that is 3 mm in diameter. The thigh is non-tender. All joints are non-tender and non-swollen. His neck is supple without lymphadenopathy. The remainder of his exam is unremarkable.

No laboratory tests are performed. The skin lesion is diagnosed as erythema migrans (EM), and a diagnosis of Lyme disease is made. He is judged to have early localized infection. He is treated with amoxicillin, 50 mg/kg/day po divided tid for 21 days. His headache and myalgia resolve within one week, and the EM resolves completely by the end of amoxicillin treatment.


A zoonosis is a disease of animals that may be transmitted to man. A vector is a carrier that transfers an infectious agent from one host to another. Lyme disease is the most common vector-borne zoonosis in the United States and is caused by the spirochete Borrelia burgdorferi. It is a multisystem, multistage, inflammatory illness affecting primarily the skin, nervous system, heart and joints. If you have difficulty remembering this, note that these affected systems are identical to those affected in rheumatic fever.

Lyme disease was recognized as a distinct disease in 1977 after a group of children in Old Lyme, Connecticut was diagnosed as having "juvenile rheumatoid arthritis". Two mothers of children with arthritis contacted the Connecticut State Department of Health and reported the occurrence of arthritis in 12 children in Old Lyme; of these, 4 lived on the same street. The mothers also reported arthritis in several members of their families and in families living in the neighboring towns of Lyme and East Haddam. An epidemiologic investigation was begun and has resulted in the knowledge of Lyme disease today.

B. burgdorferi is transmitted to humans by the ticks of the Ixodes ricinus complex. I. scapularis (the black-legged or deer tick) is the vector in the eastern United States, while I. pacificus (the western black-legged tick), transmits B. burgdorferi in the western United States (1). In the spring, the adult ticks lay eggs, from which larvae emerge. On the east coast of the United States, the larvae become infected when they feed on the reservoir, the asymptomatically-spirochetemic white-footed mouse. Since the spirochete infection is not transmitted from mother tick to their eggs, the tick larvae are not infected until they feed on this mouse. On the west coast, Lyme disease occurs sporadically, due to the fact that I. pacificus larvae feed more often on non-spirochetemic lizards than on white-footed mice (1). In the nymphal stage, the ticks feed predominantly in the spring and early summer, and two-thirds of cases of Lyme disease cases are reported from July to October. It is the nymphal stage that transmits the infection most often to humans. Since the nymphs are small, they often go undetected. The adult tick survives the winter by attaching to a host mammal, which is not involved in the life cycle of the spirochete, but merely allows the tick to survive over the winter (1). If white-tailed deer live in the environment, they are the host of choice; however at least 30 types of wild mammals and 49 species of birds may be host to the tick (2).

The number of cases reported annually has increased approximately 25-fold since national surveillance was begun in 1982 (1). During 1993-1997, a mean of 12,451 cases were reported by states annually to CDC. In the United States, the disease is primarily localized to states in the northeastern, mid-Atlantic, and upper north-central regions, and to several areas in northwestern California. Most cases of Lyme disease result from exposure to infected ticks during activities such as property maintenance, recreation, and leisure activity. Therefore persons who live or work in wooded areas or areas with overgrown brush infested with vector ticks are at risk for acquiring Lyme disease.

The B. burgdorferi spirochete is transmitted by infected ticks, which transmit the organism into the blood vessels in the skin of its host. The tick must attach to the host for 48 to 72 hours for the risk of transmission of B. burgdorferi to become substantial (3). The majority of patients with Lyme disease do not recall a tick bite, which means that with an unrecognized tick bite, these individuals are at greater risk to acquire Lyme disease, because unrecognized ticks may feed longer (3).

The incubation period from infection to onset of symptoms is 7 to 14 days, with a range of 3 to 30 days. B. burgdorferi spreads locally into the skin from the site of the tick bite, which results in a single EM lesion in approximately two-thirds of patients who become symptomatic. Days to weeks later, the spirochete may disseminate via lymphatic or blood-borne routes to other areas of the skin, causing multiple EM lesions, and to the eye, muscle, bone, synovial tissue, central nervous system and heart (2,3,4).

Lyme disease occurs in stages, and this is useful to remember when considering the diagnosis (2,3,4). The stages are: early localized (stage 1); early disseminated (stage 2); and late disseminated (stage 3).

Early localized infection (stage 1) occurs 3 to 32 days after the tick bite (3). It usually manifests as the characteristic EM rash, and may be accompanied by fever, malaise, headache, fatigue, myalgia, and arthralgia. EM by itself is diagnostic of Lyme disease, and a positive Lyme serology is not required. Indeed, most patients have negative serology in this stage (3). Thirty to fifty per cent of persons with evidence of recent infection are asymptomatic (3). The rash is usually annular, spreading from a central lesion, which is the tick bite. It may be solidly erythematous, may be a target lesion, or may have a vesicular or necrotic center. The rash may be pruritic, painful, or asymptomatic. Without treatment, the rash expands in size; hence the name migrans. The average size is 15 cm, however the lesions may be as large as 30 cm in diameter (4). A patient may have multiple EM lesions.

Early disseminated infection (stage 2) begins 3-10 weeks after the appearance of the EM lesion (3,4). Patients may develop secondary EM lesions which are not at the site of the tick bite. These lesions are often accompanied by the same systemic symptoms as primary EM. Focal neurologic involvement, the most common of which is isolated seventh cranial nerve or (Bell's palsy), is also a manifestation of early disseminated disease. This may be the presenting, as well as the only, manifestation of Lyme disease and is relatively common, affecting about 3% of children (3). Antibiotic treatment has no effect on the clinical course of the Bell's palsy, which completely resolves in 2 to 8 weeks. Lyme-related Bell's palsy should not be treated with corticosteroids (3). Other complications in stage 2 may be aseptic meningitis, carditis, radiculoneuropathy, lymphadenopathy, conjunctivitis, neck pain, fever, headache, arthralgia, myalgia, and fatigue. Radiculoneuropathy is more common in European adults, but is also seen in children in the United States (3,4).

If the patient is untreated or is inadequately treated, late-disseminated (stage 3) Lyme disease may develop 2 to 12 months after the tick bite (2,3,4). The most common manifestation of late disseminated Lyme disease in children is arthritis. Large joints are affected most often, with the knee being involved in >90% of cases (3). The involved joint is tender, erythematous and swollen; however the clinical findings are not as marked as in bacterial arthritis. With treatment, the joint shows signs of improvement in 4 to 7 days, with complete resolution in 2 to 6 weeks. Occasionally symptoms will recur after treatment, requiring another course of antibiotics. Chronic arthritis occurs primarily in patients with DR-2, DR-3, or DR-4 HLA types (2).

The most common mistake in diagnosis, is the overdiagnosis of Lyme disease by obtaining Lyme serology in patients who have vague, nonspecific symptoms, but who do not have risk factors for Lyme disease (i.e., patients who do not live or work in heavily wooded areas or areas that have dense underbrush infested with vector ticks and who do not have frequent or prolonged exposure to tick-infested habitats) (5). The ELISA serologic test for Lyme disease has high sensitivity but low specificity, and positive results in patients at low risk of disease are likely to be false positive results. At this time, diagnostic tests, including the polymerase chain reaction, based on the identification of antigens or DNA of B. burgdorferi lack sufficient specificity or sensitivity to be clinically useful (3).

Early and uncomplicated infections in children and adolescents usually respond well to orally administered antibiotics (3,4,6). Treatment of Lyme disease is outlined in Table 1. Parenteral antibiotics are generally recommended for treating meningitis, carditis, later-stage neurologic Lyme disease, and complicated Lyme disease arthritis. Late, complicated Lyme disease may respond slowly or incompletely, and more than one antibiotic treatment course may be required to eliminate active infection (2).

Table 1. Treatment of Lyme Disease (3)

Stage 1 - Early localized disease (EM):

Children <9 years old: amoxicillin, 50 mg/kg/day po divided tid (maximum dose 500 mg/dose) for 21days.

Children >9 years old: doxycycline, 100 mg po bid for 21 days. Alternatives for those who cannot take amoxicillin or doxycycline include: cefuroxime axetil, 30-50 mg/kg/day po divided bid (maximum dose 500 mg/dose) for 21 days, or erythromycin, 30-50 mg/kg/day po divided qid (maximum dose 250 mg/dose) for 21 days.

Stage 2 - Early disseminated disease:

Uncomplicated: Treat as for EM

Bell's palsy or other cranial nerve palsy: Treat as for EM, but for 21-30 days. Do not use corticosteroids.

Carditis: Treat as for late neurologic disease.

Meningitis: Treat as for late neurologic disease

Stage 3 - Disseminated disease:

Neurologic disease with isolated cranial nerve palsy: Treat as for EM but for 21-30 days.

Other: ceftriaxone 50-80 mg/kg/day in a single dose (maximum dose 2 g) for 14-21 days IV or IM; or penicillin G, 200,000-400,000 units/kg/day (maximum 20 million units/day) divided q 4 hrs, for 14-21 days IV.

Arthritis: Initial treatment same as for EM except treat for 30 days. If symptoms recur or fail to resolve after 2 months, then treat as for late neurologic disease. Some experts give a second course of oral antibiotics before using a parenteral agent.

The prognosis for Lyme disease in children and adolescents is excellent. Gerber et al. (6) reported a prospective, longitudinal, community-based cohort study of children with Lyme disease in southeastern Connecticut which studied 201 children enrolled over a period of 20 months, with a mean age of 7 years and a range of 1 to 21 years. All but 3 of the 201 patients were treated for 2 to 4 weeks with conventional antibiotic therapy, which was administered orally in 96% of cases. All had prompt clinical responses. After 4 weeks, 94% were completely asymptomatic. At follow-up, a mean 25.4 months later, none of the patients had evidence of either chronic or recurrent Lyme disease. Six patients subsequently had a new episode of EM. No patient progressed from early to late disease.

Parents may fear that their children and adolescents will acquire complications from Lyme disease that are debilitating, chronic, or fatal (6). They may question whether orally administered antimicrobials can be as effective as intravenously administered antimicrobials. In addition, if a child or adolescent later has vague, nonspecific symptoms after completing an appropriate course of antimicrobials, parents often worry that the antimicrobial therapy has been inadequate and request that additional antimicrobial therapy be prescribed. The information gathered by Gerber et al. can be used to reassure parents that Lyme disease in children and adolescents has an excellent prognosis and responds well to appropriate antimicrobial therapy.

Prevention is best achieved by avoidance of tick habitats. Whenever possible, persons should avoid areas that are likely to be infested with ticks, particularly in spring and summer when nymphal ticks feed. Ticks favor a moist, shaded environment, especially that provided by leaf litter and low-lying vegetation in wooded, brushy or overgrown grassy habitats (1).

Persons who are exposed to tick-infested areas should wear light-colored clothing so that ticks can be spotted more easily and removed before becoming attached. Wearing long-sleeved shirts and tucking pants into socks or boot tops can help keep ticks from reaching the skin. Applying insect repellents containing DEET (n,n-diethyl-m-toluamide) to clothes and exposed skin, and applying permethrin, which kills ticks on contact, to clothes, should also help reduce the risk of tick attachment. Because transmission of B. burgdorferi from an infected tick is unlikely to occur before 36 hours of tick attachment, daily checks for ticks and their prompt removal will help prevent infection (1).

The number of ticks in endemic residential areas can be reduced by removing leaf litter, brush, and woodpiles around houses and at the edges of yards, and by trees and brush to admit more sunlight, thus reducing deer, rodent, and tick habitats. Tick populations have also been reduced by applying pesticides to residential properties.

In general, antibiotic prophylaxis after a tick bite is not recommended. Persons who are bitten by a deer tick should remove the tick and seek medical attention if any of the signs and symptoms of Lyme disease develop (1,4).

A vaccine consisting of recombinant B. burgdorferi outer-surface lipoprotein A (OspA) with adjuvant (LYMErix) was licensed by the U.S. Food and Drug Administration for use in the United States in 1998. A placebo-controlled trial of the vaccine revealed that pain at the injection site was the most common side effect, reported by 24% of vaccine recipients vs. 8% of controls (7). The efficacy of the vaccine in protecting against symptomatic Lyme disease was 49% in the first year (after the first 2 doses) and 76% in the second year (after the third dose). Vaccine efficacy in preventing asymptomatic B. burgdorferi infection was 83% in the first year and 100% in the second year (7).

The cost effectiveness of vaccinating against Lyme disease has been analyzed by Meltzer et al. (8). A single answer regarding the cost effectiveness of vaccinating a person against Lyme disease cannot be calculated. The tables and figures in the study by Meltzer et al., also reprinted in the MMWR (1), will assist physicians, health care decision makers, and public health authorities to determine the cost effectiveness of vaccination for their specific situations.

Assessing the risk for Lyme disease (1) This is primarily determined by the following:

1. Density of vector ticks in the environment, which varies by place and season.

2. Prevalence of B. burgdorferi infection in vector ticks.

3. Extent of person-tick contact, which is related to the type, frequency, and duration of a person's activities in a tick-infested environment.


Questions

1. True/False: Over 90% of children with Lyme disease can be treated successfully with oral antibiotics.

2. True/False: Children with Bell's palsy should be treated with corticosteroids.

3. True/False: Multiple EM lesions are a sign of late disseminated Lyme disease.

4. True/False: Lyme vaccine is recommended for persons aged 15-70 years whose exposure to a tick-infested habitat is frequent and prolonged.

5. True/False: If a patient has an EM lesion, a diagnosis of Lyme disease can, and should, be made without serologic testing.

6. True/False: Most patients with Lyme disease do not recall having had a tick bite.

7. True/False: Patients with uncomplicated early disseminated disease should receive 30 days of antibiotics.

8. True/False: Lyme vaccine is a live-virus vaccine.

9. True/False: Lyme disease occurs most commonly in spring and summer, when nymphal ticks feed.

10. True/False: Lyme serology is so highly specific that positive results always predict the presence of Lyme disease, even in patients at low risk for the disease.

11. True/False: The number of cases reported annually has increased approximately 25-fold since national surveillance was begun in 1982.


References

1. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Recommendations for the use of Lyme disease vaccine. MMWR 1999;48(No.RR-7):1-25.

2. Steere AC. Lyme disease. New Engl J Med 1989;321:586-596.

3. Shapiro ED. Borrelia burgdorferi (Lyme disease). In: Long SS, Pickering LK, Prober CG (eds). Principles and Practice of Pediatric Infectious Diseases, first ed. 1997, New York, NY: Churchill Livingston, pp. 1061-1067.

4. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet 1998;352:557-565.

5. Steere AC, Taylor E, McHugh GL, Logigian EL. The overdiagnosis of Lyme disease. JAMA 1993;269:1812-1816.

6. Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in southeastern Connecticut. New Engl J Med 1996;335:1270-1274.

7. Steere AC, Sikand VJ, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. New Engl J Med 1998;339:209-215.

8. Meltzer MI, Dennis DT, Orloski KA. The cost effectiveness of vaccinating against Lyme disease. Emerg Infect Dis 1999;5:1-8.


Answers to questions

1. True.

2. False. Bell's palsy due to Lyme disease should NOT be treated with corticosteroids.

3. False.

4. True.

5. True.

6. True.

7. False.

8. False.

9. True.

10. False. Positive Lyme serology in low risk cases are usually false positives.

11. True


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