AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Lyme disease is the most common tick-borne illness in the United States. It was first described in the 1970s as an outbreak of arthritis in Lyme, Conn, and it was formally described in the medical literature in 1976. Since its description, the number of reported cases has increased dramatically over the last decade, probably related to the awareness of clinicians and patients in endemic areas.

Pathophysiology

Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted by Ixodid species of tick, mostly Ixodes scapularis (the common deer tick). The life cycle of Ixodid ticks occurs over 2 years. The adult lays eggs in the spring, and the larvae emerge in the summer. The larvae feed on a wide variety of small animals (eg, the white-footed mouse) that serve as important reservoirs for B burgdorferi. The following spring, the larvae emerge as nymphs that again mainly feed on small animals. The nymphs molt into adults the following fall and spend the winter feeding on larger animals, most notably the white-tailed deer. The ticks can acquire B burgdorferi during any of its 3 stages. Lyme disease is passed to humans mostly by the nymphs because they are more abundant than adult ticks during the outdoor months, and nymphs are more difficult to detect because of their smaller size.

The transmission of B burgdorferi from an infected tick to a human depends on the length of exposure. It takes hours for the tick to fully attach, and experimental studies have indicated that nymphs must feed 36-48 hours and adults 48-72 hours to transmit B burgdorferi. After B burgdorferi is introduced into the skin, it spreads locally. The local spread leads to erythema migrans (EM), a rash that is found in approximately two thirds of cases.

Over a wide range of time (days to months), the spirochete may invade the blood stream, leading to disseminated disease. Dissemination to the skin can manifest as multiple EM. B burgdorferi can spread to any tissue but commonly affects the skin, eye, muscle, heart, and central nervous system. Arthritis is a characteristic of late disease and is caused by persistence of organisms in the synovium. Some patients appear to have persistent symptoms after adequate antimicrobial treatment, suggesting an autoimmune component to chronic symptoms.

Frequency

United States

Approximately 12,000 cases occur in the United States annually. Incidence is highest in children aged 5-10 years. The 3 distinct regions in the United States are (1) the Northeast (from Massachusetts to Maryland), (2) the upper Midwest (especially Minnesota and Wisconsin), and (3) the West Coast (especially northern California).

Based on the life cycle of the tick in the United States, onset of illness is between May and October, with most cases presenting in June and July.

International

Lyme disease occurs throughout the world. In Europe, most Lyme disease is reported by Scandinavian countries, Germany, Austria, and Switzerland.

Mortality/Morbidity

The prognosis for Lyme disease generally is excellent when patients are treated early with appropriate antibiotic regimens. For patients with chronic symptoms post infection, randomized controlled trials of extended antibiotic regimens have not shown any efficacy.

CLINICAL

Section 3 of 10  

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

History

Most patients with Lyme disease do not recall a tick bite. The presenting signs and symptoms depend on the stage at which the disease is recognized, as follows:

• Early disease - Usually 7-14 days after a tick bite
• • EM: Two thirds of patients with Lyme disease present with the typical rash, EM. The rash may be a confluent patch of erythema or may have central clearing. The rash typically expands over days and is not evanescent.
  • During early disease, with or without the rash, patients may complain of fever, chills, myalgias, arthralgias, headache, and malaise. In the area of the tick bite, tender adenopathy may be noted.
• Early disseminated disease - Usually develops 3-10 weeks after inoculation. Approximately 25% of individuals infected with B burgdorferi have signs and symptoms of disseminated disease at presentation.
• • Multiple EMs are relatively small erythematous macules (1-5 cm) and often are oval. Unlike primary single EMs, these lesions can be evanescent and do not show the typical expansion over days.
  • Patients with early disseminated disease may complain of fever, myalgias, arthralgias, malaise, and headache. Persistent headache alone is a rare presentation of Lyme disease but should be considered in patients in endemic areas during summertime.
  • Aseptic meningitis may develop at this stage.
  • Cranioneuropathies, especially peripheral seventh nerve (Bell palsy), are common (3% of Lyme disease)
  • Encephalitis is rare.
  • Carditis may present as complete heart block.
• Late disease - Weeks to months after inoculation
• Arthritis is the hallmark of late disease. It tends to involve large joints (knee involved in 90% of cases). Arthritis needs to be differentiated from arthralgia, which is common in early disease.
• Most patients presenting with late disease do not have a history of EM because the rash would have led to earlier treatment and, therefore, prevention of late disease.

Physical

• Early disease
• • EM rash
    • Confluent or central clearing
    • Expands over days
    • Not evanescent
    • More common on head or neck in young children and on extremities in older children
    • Characteristic round or oval shape, which may be more difficult to recognize on the face, neck, or axilla
  • Fever
  • Myalgias
  • Malaise
  • Arthralgia
  • Uncomfortable appearing from headache or myalgias
  • Tender adenopathy (local, not diffuse)
• Early disseminated disease
• • Multiple EMs
    • Twenty-five percent of patients with Lyme disease present with multiple EM.
    • Eighty-nine percent of patients with disseminated Lyme disease present with at least one EM lesion.
  • Fever
  • Tender adenopathy (regional or generalized)
  • Conjunctivitis (uncommon, never prominent)
  • Carditis (usually manifests as heart block)
  • Meningismus as a sign of aseptic meningitis
  • Cranioneuropathy, especially cranial nerve VII and Bell palsy (peripheral seventh nerve palsy with decreased unilateral function, including the forehead)
• Late disease
• • Arthritis is located mostly in large joints, especially the knee.
  • Warmth, swelling from effusion, and limited range of motion help distinguish arthritis from simple arthralgia.

Causes

Lyme disease is caused by the spirochete B burgdorferi, which is transmitted by Ixodid species of tick, mostly Ixodes scapularis (the common deer tick).

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Myositis

WORKUP

Section 5 of 10  

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

Lab Studies

• CBC: WBC count can be normal or elevated.
• Erythrocyte sedimentation rate usually is elevated.
• Serum glutamic-oxaloacetic transaminase (SGOT) may be elevated.
• C3 and C4 generally are normal or slightly elevated.
• Antinuclear antibody (ANA) and rheumatoid factor test results are negative.
• Microscopic hematuria and mild proteinuria also have been described.
• Joint fluid in patients with arthritis may have 25,000-125,000 WBCs per mm³, often with a polymorphonuclear predominance.
• Cerebral spinal fluid (CSF) in patients with meningitis has mild pleocytosis (<1000 cells per mm³) with lymphocyte predominance.
• Diagnosis can be made clinically in the early stages of disease by the presence of EM rash.
• Culturing B burgdorferi is impractical; the organism is difficult to culture and requires an invasive procedure, such as biopsy or lumbar puncture, to obtain adequate samples.
• Serology is the standard of diagnosis in later stages of the disease.
• • Reported specificity of Lyme serology is only 90-95%. Therefore, the positive predictive value of the test is highly dependent on the prevalence of disease. Lyme serology should not be performed in children with nonspecific symptoms and no history of exposure or in children in nonendemic areas.
  • Antibodies are known to persist for many years despite eradication of the infection. Hence, diagnosis of repeat infection or evidence of cure can be difficult based on serology alone.
• Serology should include a two-step process. First, perform enzyme-linked immunosorbent assay (ELISA) or immunofluorescent assay (IFA) and, if positive, go to the second step. This next step involves Western blot analysis against specific antigens. This step is not interpretable in the absence of a positive ELISA or IFA result. Most assays require immunoglobulin against at least 3 specific proteins (for immunoglobulin M [IgM]) or 5 specific proteins (for immunoglobulin G [IgG]) for results to be considered positive. Patients with early Lyme disease who are treated with antibiotics may never develop positive titer results.
• • Early disease: Only one third of patients have a positive titer result; therefore, clinicians rely on the presence of the rash to make the diagnosis. For patients without an EM rash but in whom Lyme disease is suspected, serial titers eventually can be used to confirm the diagnosis.
  • Early disseminated disease: Ninety percent of patients have a positive titer result.
  • Late disease: One hundred percent of patients have a positive titer result.
• Polymerase chain reaction (PCR) testing is not recommended because of unacceptable low sensitivity, especially from the CSF (does have high specificity if test is positive).
• CSF titers to B burgdorferi need to be performed and interpreted at a reference laboratory. CSF titers should not be used for diagnosis of Lyme meningitis but may have value in patients who have recurrent infection or for following serial markers in patients with persistent symptoms.

Procedures

• Lumbar puncture: In cases of cranioneuropathy, it is controversial whether all patients require lumbar puncture before treatment. Occasionally Lyme disease presents as pseudotumor cerebri; an opening pressure is essential for diagnosis.
• • Currently, in most patients with isolated Bell palsy and no associated signs of aseptic meningitis, most physicians do not perform a lumbar puncture. For most other patients with cranioneuropathies and suspected Lyme disease, a lumbar puncture should be performed; CSF pleocytosis leads to treatment as indicated for CNS Lyme disease.
  • Obtain a CT scan or MRI before the lumbar puncture if increased intracranial pressure or mass lesion is suspected. Occasionally, Lyme disease presents as pseudotumor with frank papilledema; imaging should be done prior to LP in these cases.
• Joint aspiration for diagnostic reasons is unnecessary if only Lyme disease is suspected (and not septic arthritis or another etiology of effusion).

TREATMENT

Section 6 of 10  

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

Medical Care

• Treatment for all stages of Lyme disease requires antibiotics (see Medication). Facial nerve palsies improve without treatment; however, antibiotic therapy should prevent late disease. Similarly, arthritis improves without treatment but tends to recur in the same joint or other new joints.
• Administer antibiotic therapy to patients who develop a flulike illness within 3 weeks postexposure to a deer tick (in an area endemic for Lyme disease). Beyond 3 weeks, serological testing is appropriate.
• Postexposure prophylaxis has some efficacy in an adult study. A single dose of doxycycline within 72 hours of tick bite decreased development of Lyme disease. This has not been studied in children, but many clinicians have extrapolated the findings to exposed children.

Consultations

• For equivocal diagnoses or prolonged/recurrent symptomatology after seemingly adequate treatment, an infectious disease consultation may be necessary.
• Rheumatology consultation may be indicated for chronic arthritis.

MEDICATION

Section 7 of 10  

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

The antibiotic regimen depends on the stage and manifestations of the disease.

Drug Category: Antibiotics

The goal of pharmacotherapy with antibiotics is to reduce morbidity and prevent complications. Antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

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

Deterrence/Prevention

• The best prevention is education and awareness. Long pants and socks should be worn when in areas of likely tick exposure. Parents of children in endemic areas must be vigilant to check for ticks (especially the nymphs because of their smaller size) from the spring to the fall. Checking inside skin folds, behind ears, the umbilicus, groin, axilla, hairline, and scalp must be routine. Through education, parents can recognize early symptoms and signs.
• Insecticides, sprayed on clothing or directly on the skin, can deter ticks, but use of these agents must be weighed against toxicity from overzealous application.
• A Lyme disease vaccine was previously available but was subsequently removed from the market for concerns of efficacy and side effects. The vaccine was made of recombinant outer surface protein A (OspA). Newer vaccines are being developed.
• Prophylactic antibiotics after any tick exposure are not recommended. Even in endemic areas, the risk of transmission from a tick is estimated to be 1-2%. In hyperendemic areas, a single dose of doxycycline (adults) has been shown to decrease development of disease if given within 72 hours of tick bite.
• Preventing exposure and removing ticks promptly is a much better strategy. In an endemic area, prolonged attachment, a concerned parent, or pregnancy may change this approach. For a known tick exposure, a thorough search for other ticks is necessary. Following discovery of an attached tick, education about symptoms and signs of Lyme disease is the most appropriate treatment.

Complications

• One nonmedical complication of Lyme disease has been the public and media's misconceptions about the disease. Unfortunately, many clinicians perform too many tests when the prior probability of disease is low; therefore, many false-positive tests results are obtained. The combination of nonspecific symptoms and suboptimal test results has led to overtreatment for suspected (but not proven) Lyme disease and to the concept of refractory Lyme disease. In every endemic area, some physicians have capitalized on the hysteria by offering nontraditional testing and treatment and convincing parents that all ailments (behavioral, academic, medical) are related to the elusive spirochete.
• Co-infection with agents responsible for babesiosis and ehrlichiosis has been described because of the common tick vector. Acute infection caused by these agents is more common in asplenic individuals (babesiosis) or older adults (Ehrlichia); however, unlike B burgdorferi, chronic infection by these agents is not observed. To add to the confusion, ehrlichial infection may cause a false-positive result for Lyme disease on IgM Western blot analysis.

Prognosis

• The prognosis of all stages of Lyme disease is excellent with appropriate antibiotic treatment. Symptoms of arthritis may persist for a few weeks beyond adequate therapy; therefore, retreatment usually is not necessary unless symptoms worsen or persist beyond 2 months.
• Unfortunately, antibodies induced by the infection are not protective against further exposures to B burgdorferi; therefore, reinfection easily could be confused with a recurrence. Because antibodies may persist for years following an infection, repeat infection is a difficult diagnosis without specific signs of Lyme disease (eg, EM rash). Increasing titers after adequate treatment certainly creates suspicion of an active infection.
• Some individuals with arthritis may have persistent symptoms beyond the clearance of the infection. This phenomenon most likely is related to autoimmunity and is more prevalent among individuals with HLA-DR2, HLA-DR3, or HLA-DR4 allotypes.

Patient Education

• Primary care providers should educate parents and children who live in endemic areas about the risk of Lyme disease. Discuss prevention measures with them. Focus post–tick exposure counseling on watching for symptoms and signs of Lyme disease.
• For excellent patient education resources, visit eMedicine's Bites and Stings Center and Muscle Disorders Center. Also, see eMedicine's patient education articles Lyme Disease, Ticks, Chronic Fatigue Syndrome, and Chronic Pain.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• The diagnosis of Lyme disease is difficult without specific signs because of the limitations of current diagnostic tests (especially in early stages of the infection).
• Test patients with aseptic meningitis, facial nerve palsy, or arthritis for Lyme disease if they live or have traveled to an endemic area.
• Diagnosis of reinfection or recurrent infection is complicated by the persistence of antibody beyond the eradication of disease.
• Because testing is related to stage of disease combined with a 2-stage test, laboratory results are often misinterpreted. Clinicians unfamiliar with Lyme disease or Lyme testing may falsely exclude diagnosis (early disease) or falsely diagnose disease (old antibody or using Western blot in those with negative ELISA test results).

REFERENCES

Section 10 of 10

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

• Avery RA, Frank G, Glutting JJ. Prediction of Lyme meningitis in children from a Lyme disease-endemic region: a logistic-regression model using history, physical, and laboratory findings. Pediatrics. Jan 2006;117(1):e1-7. [Medline].
• Edlow JA. Lyme disease and related tick-borne illnesses. Ann Emerg Med. Jun 1999;33(6):680-93. [Medline].
• Gerber MA, Zemel LS, Shapiro ED. Lyme arthritis in children: clinical epidemiology and long-term outcomes. Pediatrics. Oct 1998;102(4 Pt 1):905-8. [Medline].
• Halsey NA, Abramson JS, Chesney PJ. American Academy of Pediatrics. Committee on Infectious Diseases. Prevention of Lyme disease. Pediatrics. Jan 2000;105(1 Pt 1):142-7. [Medline].
• Kaplan RF, Trevino RP, Johnson GM. Cognitive function in post-treatment Lyme disease: do additional antibiotics help?. Neurology. Jun 24 2003;60(12):1916-22. [Medline].
• Krupp LB, Hyman LG, Grimson R. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. Jun 24 2003;60(12):1923-30. [Medline].
• Moses JM, Riseberg RS, Mansbach JM. Lyme disease presenting with persistent headache. Pediatrics. Dec 2003;112(6 Pt 1):e477-9. [Medline].
• Nadelman RB, Nowakowski J, Fish D. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. Jul 12 2001;345(2):79-84. [Medline].
• Seltzer EG, Shapiro ED, Gerber MA. Long-term outcomes of lyme disease. JAMA. Jun 21 2000;283(23):3068-9. [Medline].
• Shapiro ED. Lyme disease. Pediatr Rev. May 1998;19(5):147-54. [Medline].
• Steere AC. Lyme disease. N Engl J Med. Jul 12 2001;345(2):115-25. [Medline].
• Vazquez M, Sparrow SS, Shapiro ED. Long-term neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease. Pediatrics. Aug 2003;112(2):e93-7. [Medline].

Article Last Updated: Mar 27, 2006