AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

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

Background

Lyme disease (LD) is a vector-borne, multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi sensu lato. It is transmitted to humans by infected ticks of the Ixodes genus. LD is endemic in North America, Europe, and Asia, and the distribution of the vectors directly affects the incidence of the disease. Ixodes scapularis is the principal vector found in Northeastern and Central United States and Canada, while Ixodes pacificus is more common on the Pacific coast. Ixodes ricinus is the principal vector in Europe. The vector in Asia is the taiga tick, Ixodes persulcatus.

In the 1920s, Garin and Bujadoux described a patient with meningoencephalitis, painful sensory radiculitis, and erythema migrans following a tick bite, and they postulated the symptoms were due to a spirochetal infection. In the 1940s, Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions. In the United States, the syndrome identified as LD gained popular recognition in 1975, when several children in Old Lyme, Connecticut, developed a syndrome mimicking juvenile rheumatoid arthritis.

The clinical manifestations of LD generally follow 3 stages of disease progression: early localized, early disseminated, and chronic disseminated. All are potentially curable with antibiotic therapy. The infection progresses to disseminated disease in approximately 50% of untreated patients.

Pathophysiology

The infectious cycle of B burgdorferi involves colonization, infection of Ixodes ticks, and transmission to broad a range of mammalian hosts, including humans. Variation in environmental and host conditions promotes different gene expression and changes in the composition of the membrane proteins of the spirochete. This adaptation is a critical step in the pathogenesis and transmission of LD.

The Ixodes tick progresses through 4 stages of development: egg, larva, nymph, and adult (see Image 1). Only larvae, nymphs, and adult female ticks require blood meals, and only ticks in the nymphal and adult stages can transmit B burgdorferi. The risk of LD is highest during the time of the year when the nymphal stage is seeking a blood meal.

Ticks feed in a seasonal pattern, with larvae feeding in the late summer, nymphs feeding in the following spring and summer, and adults feeding in the fall. Ixodes ticks acquire B burgdorferi by feeding on an infected animal host. The white-footed mouse is the preferred feeding source of nymphs, and it is an important reservoir of B burgdorferi in the United States. Although the prevalence of B burgdorferi infection in adult ticks is twice that of nymph ticks, nymphs are responsible for 90% of human disease transmissions because of the great abundance of nymphs, the increase in human outdoor activity in the summer (peak feeding season of nymphs), and the relative ease with which large adult ticks are detected and removed.

Ticks carry B burgdorferi organisms in their midgut. Disease is transmitted to humans as the spirochete is translocated from the gut to the salivary glands and then to the person at the site of the bite. B burgdorferi then invades the surrounding local tissue and undergoes hematogenous dissemination. After entering the circulation, the organism invades the cutaneous, synovial, cardiac, and nervous systems. Spirochetes have also been demonstrated histologically in bone marrow, the spleen, lymph nodes, the liver, testes, and the placenta during early hematogenous dissemination.

The effects of B burgdorferi infection in humans are related to direct invasion by the organism (eg, erythema migrans) or to a secondary inflammatory reaction. Antibodies against spirochetal protein membrane epitopes have been shown to cross-react with neural and connective tissues. This molecular mimicry possibly generates an autoimmune inflammatory reaction. The pathophysiology of early versus late manifestations of the disease is similar to that seen with syphilis.

Frequency

United States

LD is the fastest growing vector-borne disease in the United States, with more than 40,000 cases reported during 2001-2002. Most of the states in the United States have reported LD. The areas with higher incidences are northeastern (Massachusetts to Maryland), midwestern (Minnesota and Wisconsin), and western (Oregon and California) states. The reported prevalence is 4.4 cases per 100,000 persons. More LD cases are probably being reported now because of enhanced physician awareness and sophisticated laboratory surveillance. In addition, urban expansion into formerly wooded habitats has increased the incidence of LD as more people than before are living near tick-infested fauna.

The incidence of LD-related neurologic manifestations is broadly described in the literature. One group reported the following frequencies of neurologic involvement: cranial neuritis in 50-60%, radiculoneuritis in 45%, and CNS involvement in 15-20%. The same group reported the following signs and symptoms in patients with meningitis: headache in 50%, fatigue in 40%, fever or myalgia in 30%, neck stiffness in 20%, and photophobia in 10%. Other sources report that cranial neuropathies occur in 5-10% of untreated patients with LD, whereas lymphocytic meningitis develops in 10-15%.

International

Cases have been documented in eastern Ontario, Canada; Europe; Russia; China; Japan; and Australia. Infection most often occurs between May and November, with peak incidence in June and July. In a recent publication, the estimated incidence of LD was as high as 206 cases per 100,000 population in Slovenia and 135 cases per 100,000 population in Austria. Increases in prevalence have been also observed in Poland, Germany, Bulgaria, Norway, and Finland.

Mortality/Morbidity

• Approximately 80% of untreated or inadequately treated patients develop some manifestation of disseminated disease. Although such episodes are typically subacute and transient, infrequent cases of chronic, severe, and disabling disease have been described.
• Although 15-55% of patients with LD report chronic or intermittent symptoms persisting for months to years after adequate antimicrobial treatment, recent data do not support postulations of a poorly defined post-LD syndrome. Common symptoms that patients and their caregivers often attribute to previous LD include cognitive disturbances, fatigue, joint or muscle pain, headaches, hearing loss, vertigo, mood disturbances, paresthesias, and difficulty sleeping.
• Death is rarely, if ever, attributed to LD.

Sex

Both sexes are equally affected.

Age

LD can occur at any age; however, the age distribution is bimodal, with the highest incidence of infection occurring in patients aged 2-15 years and 30-55 years. In general, this pattern is related to increased levels of outdoor activity and environmental exposure in patients in these age groups.

CLINICAL

Section 3 of 11  

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• Follow-up
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History

A history of environmental exposure in an area endemic for LD (particularly wooded, brushy, or grassy habitats) aids in recognizing the infection. Endemic areas can be defined as those with established populations of vector ticks and evidence of enzootic transmission of B burgdorferi between the tick and the resident animal population. In addition, current recommendations for antimicrobial prophylaxis require that the rate of infection of the ticks with B burgdorferi should be greater than 20%. Patients are generally unaware of a tick bite because ticks are extremely small and their bites are often painless.

The 3 stages of LD are as follows:

• Stage 1 - Early localized infection (1-30 d after the bite)
• • Most patients present with a characteristic expanding rash (ie, erythema migrans) at the site of the tick bite 7-14 days after the tick is removed.
  • Approximately 50% of patients describe flulike symptoms within days to 1 week of infection.
  • Symptoms include fatigue, myalgia, arthralgia, headache, fever, chills, and neck stiffness, which may resolve spontaneously even if specific therapy is not initiated.
• Stage 2 - Early disseminated LD (weeks to months after the bite)
• • Symptoms related to early disseminated LD occur in at least half of all untreated patients.
  • One or more organ systems become involved as hematologic or lymphatic spread disseminates spirochetes to distant sites. Musculoskeletal and neurologic symptoms are the most common; less common symptoms are cardiac disturbances such as dizziness, syncope, dyspnea, chest pain, and palpitations. The most common cardiac abnormality is atrioventricular block. Fibrinous pericarditis has also been described.
  • Skin involvement can be seen in 25% of cases. Multiple secondary erythema migrans, lymphocytoma, and acrodermatitis chronicum atrophicans (ACA) are some examples.
  • Neurologic involvement, also known as Lyme neuroborreliosis, is reported in 5-20% of cases. In the United States, cranial neuropathy is the most common manifestation of early neurologic LD. Other manifestations include diffuse or focal mononeuropathy multiplex (multifocal involvement of anatomically unrelated nerves), lymphocytic meningitis, plexopathy, and/or radiculoneuropathy. Less common presentations include myositis, pseudotumor cerebri, and cerebellitis.
• Stage 3 - Chronic LD (months to years after infection and may occur after a period of latency)
• • Musculoskeletal and neurologic systems are most commonly affected.
  • Neurologic abnormalities are apparent in both the CNS and peripheral nervous system.
  • Typical presentations of late-stage neurologic LD include subacute encephalopathy, chronic progressive encephalomyelitis, and late axonal neuropathies.
  • Progressive encephalomyelitis and ACA-associated neuropathy are more common in Europe.

Physical

• Dermatologic findings
• • As many as 90% of infected patients have a characteristic expanding rash (ie, erythema migrans) at the site of the tick bite.
  • An erythematous skin lesion present while an Ixodes tick is still attached is most likely a hypersensitivity reaction rather than erythema migrans. Hypersensitivity reactions also tend produce smaller ( <5 cm) lesions, which typically begin to disappear in the first 2 days. In contrast, erythema migrans starts as a flat to slightly raised erythematous lesion at the site of the tick bite within days to weeks. Over days, the lesion spreads to a diameter of approximately 5-6 inches. The center of the bite may clear, giving this lesion its typical bull's-eye appearance (see Images 2-3). Erythema migrans can also manifest as a purpuric lesion with vesicles or pustules at the center of the primary lesion. Without therapy, erythema migrans typically fades within 3-4 weeks.
  • Several weeks to months after the initial event, multiple areas of erythema migrans occur in more than half of all untreated patients. These secondary cutaneous eruptions are similar to the initial erythematous lesions but typically are smaller, are not uniquely associated with the site of the tick bite, and are less migratory. In addition, they lack indurated centers. Secondary lesions tend to fade within 3-4 weeks. In less than 1% of patients, a small, reddish nodule or plaque (described as Borrelia lymphocytoma) may develop on the ear or nipple during stage 2 disease.
  • ACA is a relatively uncommon physical manifestation of chronic LD. This condition manifests as swelling and bluish-red discoloration of the skin on a distal extremity. Over time, the lesion typically becomes atrophic or sclerotic, appearing similar to scleroderma. One third of patients with acrodermatitis chronicum have an associated sensory polyneuropathy.
• Rheumatologic findings
• • Approximately 60% of all patients develop symptoms of intermittent migratory monoarthritis. Episodes last a mean of 3 months and almost universally affect the knee or temporomandibular joints.
  • Joint symptoms develop in approximately 80% of all untreated patients within 2 years of infection.
  • The severity of joint involvement can range from intermittent episodes of subjective pain to frank arthritis to chronic erosive synovitis.
  • The knee joints are commonly affected, although migratory oligoarthritis involving the small or large joints can occur. During the attacks, the joints are swollen, hot, and painful, but they are not usually red.
  • Although the percentage of patients with recurrent arthritic attacks decreases each year beyond infection, the duration of such episodes progressively lengthens.
  • Less than 10% of patients with arthritic sequelae develop pannus or erosion of cartilage and bone.
• Neurologic findings
• • Approximately 5-10% of untreated patient with LD have signs of cranial neuropathies, and up to 60% of patients with early neuroborreliosis develop cranial neuritis. It usually begins 3 weeks after infection. Seventh nerve palsy is by far the most common. Bilateral facial palsy can be seen in 35% of patients and is a unique characteristic that is useful for distinguishing it from idiopathic Bell palsy and other disorders. Typical associated findings depend on the nerve affected and can include visual or auditory disturbances, facial paresthesia, and/or vertigo. Multiple cranial neuropathies can occur.
  • Aseptic meningitis is relatively common, occurring in as many as 15% of untreated patients bitten by the Ixodes tick and in 30% of LD cases. Symptoms usually occur 2-10 weeks following infection. Headache, neck pain or stiffness, and photophobia typically indicate meningeal irritation. Meningitis may be accompanied by cranial or peripheral radiculoneuropathy.
  • Borrelia encephalopathy most commonly manifests as a mild confusional state accompanied by disturbances in memory, concentration, mood, sleep, personality, and/or language occurring months to years after the infection. Depression and irritability are also common. The results of cerebrospinal fluid (CSF) analysis and neuropsychiatric testing usually confirm the diagnosis. Evaluation of the CSF usually yields normal results, but some cases of elevated protein concentrations and evidence of intrathecal antibody production have been reported.
  • Borrelia encephalomyelitis is a rare but severe and slowly progressive syndrome that occurs in late disseminated disease. Symptoms can progress gradually or in a relapsing-remitting pattern, with partial improvement after the attacks. The most common clinical manifestations are hemiparesis, ataxia, seizures, cognitive impairment, bladder dysfunction, and hearing loss. Myelitis is present in 50% of patients with late neuroborreliosis. Progressive spastic paraparesis or quadriparesis is common.
  • Acute radiculoneuritis is reported in 50-85% of cases. Acute onset of motor deficits, severe radicular pain, and sensory loss are commonly seen after 2-4 weeks of infection. Multifocal asymmetric weakness is a common presentation. Although the presentation of inflammatory radiculoneuropathy is often indistinguishable from that of spinal-root compression, involvement of the thorax of multiple dermatomes and a lack of a precipitating injury can aid in diagnosis.
  • For peripheral neuropathy, patients usually report intermittent paresthesias. The most frequent finding upon examination is decreased vibratory sensation of the distal lower extremities. A "stocking glove" distribution of epicritic sensory deficits is also a common finding.
  • With late axonal neuropathy, patients can report intermittent distal limb paresthesias months to years after infection. It is distinct from the neuropathy of early LD because the symptoms are less severe. ACA-associated neuropathy is common in Europe and manifests as neuropathic pain, paresthesias, and muscle cramps.
  • In Europe, common manifestations of Garin-Boujadoux-Bannwarth syndrome (Bannwarth syndrome) include neuritic pain, cranial neuritis without headache, and lymphocytic pleocytosis. Bannwarth syndrome has also been called tick-borne meningopolyneuritis, lymphocytic meningoradiculitis, and chronic lymphocytic meningitis.
  • Neuropsychiatric findings are controversial and include manifestations of late-stage disease or post-LD syndrome, including depression, anxiety, schizophrenialike psychosis, bipolar disorder, and dementia.
• Cardiac findings
• • Approximately 8% of untreated patients have acute-onset atrioventricular conduction abnormalities.
  • Cardiac involvement ranges from atrial or ventricular arrhythmias to transient heart block or myopericarditis.
  • Most attacks are isolated and transient, lasting less than a week. In rare instances, patients with heart block require electrical pacing.
• Ophthalmic findings: Less than 5% of untreated patients have ophthalmic manifestations such as iritis, keratitis, retinal vasculitis, or optic neuritis.

Causes

• LD is caused by infection with the spirochete B burgdorferi sensu lato, which is transmitted to the host by the bite of Ixodes ticks after exposure to areas likely to harbor ticks (eg, woody, brushy, or grassy outdoor habitats).
• B burgdorferi sensu lato is a broad category of closely related but genetically distinct genospecies. These subspecies are associated with different clinical presentations, probably due to genomic variation.
• • B burgdorferi sensu stricto mainly is present in the United States, and infection with this organism has a particular predilection to affect joints.
  • Borrelia garinii is present in Europe and is responsible for many of the neurological manifestations.
  • Borrelia afzelii is present in Europe and commonly causes cutaneous manifestations, including ACA.
• Patients with HLA haplotype DR4 or DR2 and antibodies to OspA and OspB proteins in their joint fluid may be more susceptible to long-term arthritis than persons without these characteristics. The presence of these genes is related to the development of autoimmunity in the joint, which can lead to persistent inflammation even after the spirochete is apparently eradicated.

DIFFERENTIALS

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Other Problems to be Considered

Atypical facial pain
Babesiosis
Bacterial meningitis
Chronic fatigue syndrome
Dementia
Depression
Gout or pseudogout
Human granulocytic anaplasmosis (previously termed ehrlichiosis)
Infectious mononucleosis
Mononeuropathy multiplex
Plant dermatitis
Radiculopathy
Reiter syndrome
Rheumatoid arthritis
Rocky Mountain spotted fever

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory diagnosis: According to US Centers for Disease Control and Prevention surveillance criteria, patients presenting with a clinical picture compatible with early LD (ie, erythema migrans, constitutional flulike symptoms) and a history of exposure to an area in which tick exposure is likely do not require laboratory confirmation of the disease before receiving treatment. Erythema migrans is the only manifestation of LD in the United States that allows clinical diagnosis in the absence of laboratory confirmation.
• Serologic testing: Serologic testing typically involves enzyme-linked immunosorbent assay (ELISA) or immunofluorescence assay (IFA). If results from either of these tests are positive or indeterminate, Western blotting should be performed to confirm LD.
• • Seroconversion can take as long as 6-8 weeks after a tick bite. The false-negative rate for ELISA is 32% in early disease. Vaccination with the LD vaccine and a variety of diseases, including Rocky Mountain spotted fever, syphilis, systemic lupus erythematosus, and rheumatoid arthritis, can cause false-positive results. Late disease is tentatively diagnosed when at least 1 objective clinical manifestation of disseminated disease is present and is supported by ELISA or IFA results. These tests have 89% sensitivity but only 72% specificity for detecting LD.
  • A positive result on Western blotting after ELISA or IFA is an indication for treatment. Likewise, a negative result is highly suggestive of a false-positive ELISA finding, and therapy is not indicated.
  • Inadequate antibiotic therapy for early LD can suppress the antibody response, potentially yielding a false-negative result on ELISA, IFA, or Western blotting. Serum concentrations of immunoglobulin M (IgM) antibodies usually peak 6-8 weeks after infection and disappear within 4-6 months, although levels sometimes remain elevated for several months or years. IgM titers are useful in evaluating early disease and are considered positive if 2 of the 8 most common bands associated with early disease (ie, 18, 21, 28, 37, 41, 45, 58, or 93 kd) are present.
  • In patients with a high probability of having early LD, IgM testing is 96% specific and 93% predictive. Immunoglobulin G (IgG) antibodies are typically detectable within 6-8 weeks after infection, peak within 4-6 months, and remain elevated indefinitely. In late-stage disease (>4-6 wk after infection), IgG results are more useful than IgM results and are considered diagnostic if 5 of 10 IgG bands common in late disease (ie, 18, 21, 28, 30, 39, 41, 45, 58, 66, or 93 kd) are present. Careful consideration of both IgG and IgM antibodies is essential because the IgG response may be negative in as many as 50% of patients (particularly those with early disease), whereas a persistence of IgM antibodies can lead to false-positive findings in patients infected for more than 1 month who subsequently receive effective treatment. Of note, serologic results can remain positive years after adequate treatment and cannot be used to distinguish active from inactive disease.
• CSF evaluation
• • Although CSF cultures are positive in less than 10% of patients with apparent meningitis, intrathecal antibodies and a lymphocytic pleocytosis (approximately 100 cells/µL) are present in more than 80%. Patients with meningitis typically have elevated protein concentrations (>50 mg/dL) but normal glucose levels (45-80 mg/dL). Oligoclonal bands specific for B burgdorferi may be present. In patients whose clinical presentation strongly suggests neurologic involvement, CSF testing is rarely necessary because diagnostic levels of IgM or IgG antibodies in the serum alone are an indication for treatment.
  • In elusive cases, spinal tap is considered essential to evaluate the CSF for specific antibodies to B burgdorferi. The production of intrathecal anti–B burgdorferi antibodies indirectly confirms neuroborreliosis. Intrathecal antiborrelial antibody production is typically seen within 3-6 weeks of infection. To account for potential leakage of antibody across the blood-brain barrier, a CSF-to-serum index must be examined. Immunologic testing by means of Western blotting is preferred because of concerns regarding the sensitivity of ELISA. A CSF-to-serum index of greater than 1.0 suggests synthesis of antibody in the CNS. False-negative results can occur, and an intrathecal antibody response can persist for years after successful treatment.
• Advanced techniques
• • LD multiplex polymerase chain reaction (PCR)
    • Lyme multiplex PCR has not been standardized; therefore, it is not currently used in routine testing.
    • PCR is used to detect B burgdorferi DNA in the blood, CSF, urine, or synovial fluid within weeks of infection.
    • The result is positive in approximately 30% of patients with active LD.
    • A notable disadvantage of PCR testing is the likelihood of false-negative results because of a sparsity of spirochetes in infected tissues. Likewise, inexperience with the PCR technique can yield false-negative findings when care is not taken to prevent contamination and when incorrect primers are used in preparing the specimen.
    • Although most PCR results become negative within 2 weeks of antimicrobial therapy, results can remain positive for years after apparent cure.
    • One of the most compelling uses of PCR may be in confirming persistent or recurrent disease because a positive result is highly specific for exposure to B burgdorferi.
  • LD urine antigen testing: This test has not been studied sufficiently. It has not been proven reliable or accurate and therefore should not be used as a diagnostic tool.
  • Flow cytometric borreliacidal antibody test: This test is used to detect highly specific borreliacidal antibodies that formed after exposure to B burgdorferi. The specificity of borreliacidal antibody test results far exceeds those of ELISA. One study of 572 patients showed a specificity of greater than 99%, although its sensitivity is marginal, at 72%. Although borreliacidal antibodies are detectable in the serum soon after infection, the number of antibodies increases with the duration and severity of illness; therefore, borreliacidal antibody testing is most useful in late disease. It should not be performed in patients who recently received antimicrobial therapy.

Imaging Studies

• MRIs show abnormalities in approximately 15-20% of patients in the United States who have neurologic manifestations of LD.
• • Punctate lesions of the periventricular white matter are most common and resemble changes seen in demyelinating or inflammatory disorders. In an attempt to differentiate radiological manifestations of neuroborreliosis and multiple sclerosis, a recent study proposed that occult brain tissue damage (seen by brain magnetization transfer and diffusion tensor magnetic resonance) are not common in neuroborreliosis, as opposed to multiple sclerosis.
  • Space-occupying lesions have also been reported as a rare manifestation.
  • In European patients with CSF-confirmed LD, imaging findings have suggested that microvasculitis and macrovasculitis in the CNS may be responsible for neurologic sequelae and the MRI changes seen in patients with neuroborreliosis.
  • Functional brain imaging, such as single-photon emission CT scanning, may contribute to the diagnosis of chronic neurologic LD.

Other Tests

• Electrophysiologic studies: Abnormal results are often consistent with axonal degeneration in patients presenting with peripheral neuropathy in stage 3 disease.

Procedures

• Approximately 60-80% of specimens isolated from the leading edge of a suspected erythema migrans lesion by means of saline-lavage needle aspiration or 2-mm punch biopsy reveal B burgdorferi. However, because the presence of a lesion along with a compatible history and clinical presentation are sufficient to initiate treatment, these skin biopsy procedures are seldom performed. However, histological examination is recommended in patients with suspected borrelial lymphocytoma, when the location of the lesion or the clinical history is not clear to make a diagnosis.

Histologic Findings

Marked perivascular lymphocytic and plasmocytic infiltration is a key histologic finding in all affected tissues (see Image 4). Lymphocytoma is characterized by marked lymphocytic infiltration replacing or nearly replacing the dermis.

TREATMENT

Section 6 of 11  

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Medical Care

• The goals of treatment are to cure B burgdorferi infection, to speed the resolution of the clinical manifestations, and to prevent complications.
• • The antibiotic regimen is based on the stage of disease, the clinical manifestations, and the patient's characteristics.
  • The selection of pharmacologic modality should always be based on the patient's allergies, age, and concomitant medical conditions.
  • Of great importance, doxycycline is contraindicated in patients younger than 8 years and in pregnant women.
  • Doxycycline, amoxicillin, or cefuroxime axetil for 14-21 days is indicated for early localized or early disseminated disease associated with erythema migrans in the absence of neurologic involvement or third-degree heart block. This regimen is also recommended for patients with cranial nerve palsy with normal CSF findings and those with borrelial lymphocytoma.
  • Cefuroxime axetil is effective; however, because of its cost, it is reserved for patients unable to take amoxicillin or doxycycline.
  • Of note, data from a recent clinical trial indicate that 10-day treatment with doxycycline was as effective as 20-day treatment with doxycycline in patients with erythema migrans.
  • LD arthritis without neurological disease may be treated with the drugs listed above for 28 days. The preferred duration of the oral regimen for ACA is 21 days.
  • Macrolides are alternatives agents but are used only when the first-line agents are not tolerated or are contraindicated.
• Patients with acute neurologic disease manifested by meningitis or radiculopathy, those with palsy of cranial nerve VII and clinical or laboratory evidence of CNS involvement, those with arthritis with objective evidence of neurologic disease, and those with late neurologic disease should be treated with intravenous ceftriaxone for 14-28 days.
  • An alternative is intravenous penicillin G or cefotaxime.
  • Doxycycline may be used in patients intolerant of beta-lactams.

Consultations

• Consultation with a rheumatologist may be appropriate in patients with persistent arthritic sequelae despite conventional antimicrobial therapy.
• Consultation with a neurologist is recommended in patients with persistent or chronic manifestations of LD, such as chronic fatigue syndrome.

MEDICATION

Section 7 of 11  

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The goals of pharmacotherapy are to reduce morbidity, prevent complications, and eradicate the infection.

Drug Category: Antibiotic

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 11  

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• Medication
• Follow-up
• Miscellaneous
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Further Outpatient Care

• Depending on the clinical presentation, continued follow-up by the treating rheumatologist, psychiatrist, and/or neurologist may be warranted.
• Follow-up may be of particular importance in patients with the chronic sequelae of the controversial post-LD syndrome, in which symptoms may be refractory to conventional therapies.

Deterrence/Prevention

• Avoid areas that nymphal B burgdorferi-infected ticks inhabit.
• Wear appropriate clothing for outdoor exposure in endemic areas. Wear long-sleeved shirts and pants, and tuck them in whenever possible. Wear light-colored clothing, which may aid the detection of ticks. Inspect the entire body daily to locate and remove any ticks.
• Use a tick repellent containing N,N-diethyl-m-toluamide (DEET) or permethrin when exposure to an endemic environment is imminent.
• • DEET is available in 5-100% concentrations as sprays, creams, gels, lotions, solutions, towelettes, and other formulations.
  • In most circumstances, products containing 10-35% DEET are sufficient to provide adequate protection from ticks.
  • The American Academy of Pediatrics has issued a recommendation that children not be exposed to products containing more than 10% DEET because of several case reports of neurotoxicity occurring in children exposed to high concentrations. To prevent accidental exposure to the mucous membranes, DEET repellent should not be applied to children's hands.
  • The degree of protection is proportionally related to the concentration of DEET. That is, products with a high DEET concentration provide a long duration of protection. Extended-release liposphere microdispersion DEET preparations (6.5% and 10%) may decrease exposure to high concentrations of DEET while maintaining a relatively long (2-4 h) duration of activity.
  • Other proposed guidelines to reduce DEET exposure include using a minimal amount of product to cover the exposed skin and clothes; avoiding contact with mucous membranes, open cuts, or irritated skin; and washing treated areas with soap and water as soon as the person goes indoors.
• The US Food and Drug Administration approved a vaccine for LD (LYMErix Lyme disease vaccine [recombinant OspA]; SmithKlineBeecham Biologicals, Philadelphia, Pa). The vaccine was discontinued because of poor demand. Currently, no vaccine is available.
• • Previous vaccination does not alter current treatment recommendations.
  • Vaccinated individuals have positive results with ELISAs for LD antibodies but can be distinguished from those with active infection using a Western blot test.
• Prophylactic antibiotic therapy (single 200-mg dose of doxycycline) is only recommended for adults and children older than 8 years if all of the following circumstances exist:
  • The attached tick can be recognized as I scapularis (adult or nympha) and it is estimated to have been attached for more than 36 hours.
  • Prophylaxis can be started within 72 hours of the time the tick was removed.
  • Ecologic information indicates that the local rate of infection of these ticks with B burgdorferi is greater than 20%.
  • Doxycycline is not contraindicated.

Prognosis

• The prognosis for most patients receiving conventional antimicrobial therapy is excellent. A recent study of the long-term symptoms and effect on activities of daily living revealed no significant difference between patients previously treated for LD and age-matched control subjects 15-135 months after diagnosis.
• Post-LD syndromes have not been well defined. Proposed criteria include the presence of fatigue, musculoskeletal pain, and/or cognitive difficulties within 6 months of the diagnosis of LD and a persistence of symptoms for at least 6 months after completion of generally accepted antibiotic therapy. The presence of co-infections (babesiosis, human granulocytic anaplasmosis) and objective evidence of associated conditions or underlying disorders that may explain the patient's symptoms exclude the existence of a post-LD syndrome.

Patient Education

• Patients residing in areas endemic for LD should be advised to take appropriate precautions to protect themselves against tick exposure.
• Additional information can be obtained from the American Lyme Disease Foundation, Inc. Mail: PO Box 684 Somers, NY 10589. E-mail: Inquire@aldf.com.
• For excellent patient education resources, visit eMedicine's Bites and Stings Center and Arthritis Center. In addition, see eMedicine's patient education articles Lyme Disease and Ticks.

MISCELLANEOUS

Section 9 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Given the lack of specificity in the clinical presentation of LD and given the limitations of serologic testing, both misdiagnosis and underdiagnosis of LD continue to be problems.
• Unnecessary serologic testing and inappropriate therapy contribute to excessive financial costs.
• Lack of recognition of LD imposes considerable burdens on patients with chronic manifestations and their caregivers.

Special Concerns

• Pregnancy
• • Extremely rare cases of neonatal death or stillbirth have been reported after pregnancies complicated by untreated or inadequately treated symptomatic maternal Lyme borreliosis. Subsequent findings from Centers for Disease Control and Prevention studies suggest that congenital infection with B burgdorferi is unlikely and that it is not directly responsible for adverse fetal outcomes.
  • Special consideration should be given to drug therapy in pregnant women. Doxycycline is contraindicated in pregnancy (pregnancy category D) because of fetal risks, such as permanent discoloration of the teeth, enamel hypoplasia, and retardation of skeletal development.
• Co-infection
• • Co-infection with other tick-borne illnesses should be considered in patients with a poor response to conventional antimicrobial therapy or altered clinical presentations.
  • Co-transmitted infective organisms can include Babesia microti, the primary cause of babesiosis; Anaplasma phagocytophilium, the cause of human granulocytic anaplasmosis; flavivirus, the cause of tick-borne encephalitis; and Powassan or tick-borne encephalitislike virus.

MULTIMEDIA

Section 10 of 11  

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

Media file 1:  Magnified ticks at various stages of development.
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Media file 2:  Typical appearance of erythema migrans, the bull's-eye rash of Lyme disease.
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Media file 3:  Lyme rash. Courtesy of M. Fergione, B. Tucker, and L. Zernel; Pfizer Laboratories.
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Media file 4:  Photomicrograph demonstrates perivascular infiltrate in a biopsy specimen from the border of an erythema migrans lesion (hematoxylin and eosin stain). Courtesy of J. Edlow.
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REFERENCES

Section 11 of 11

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

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Article Last Updated: Mar 23, 2007