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 arthropod-related disease in the United States, Europe, and portions of Japan.

Lyme disease is transmitted by the bite of an Ixodes tick infected with Borrelia burgdorferi. Ehrlichiosis and babesiosis are also transmitted by the Ixodes tick. The disease is a multisystem spirochetal disorder that can mimic many other diseases. As in syphilis, another spirochetal illness, Lyme disease occurs in 3 stages.

The life cycle of the Ixodes tick consists of 3 stages, the larval, nymphal, and adult stages. Mice and deer most commonly are involved in this cycle, but any mammal can serve as the tick's host. The nymphal stage is the most aggressive. Ticks in this stage feed in mid to late spring. Because of their extremely small size, many people do not remember the tick bite.

Pathophysiology

The pathogenesis of Lyme disease is not well understood, but the symptoms are believed to be due to direct infection and a delayed hypersensitivity mechanism. A controversial aspect of the disease is the form of the disease known as late or chronic Lyme disease. Some patients may develop chronic or relapsing inflammation (including uveitis). It is unknown if these patients truly have Lyme disease and if they represent treatment failures, a persistence of organism, an infection with another tick borne pathogen, or an autoimmune phenomenon.

Frequency

United States

Of the cases of Lyme disease, 75% occur during the summer months. Clusters of Lyme disease occur in 3 geographic areas of the United States, as follows: the Northeast, especially southern Connecticut, Westchester County, and Long Island in the state of New York; the Midwest, in Minnesota and Wisconsin; and the Northwest, in Washington, Oregon, and northern California.

Race

No racial predilection exists.

Sex

No sexual predilection exists.

Age

With Lyme disease, there is a bimodal distribution of age groups with 2 peaks, one in children aged 5-14 years and one in adults aged 30-59 years.

CLINICAL

Section 3 of 10  

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

History

• The clinical manifestations of untreated Lyme disease occur in 3 stages.
• • Stage 1 is the localized bull's eye skin rash of erythema chronicum migrans. This pathognomonic skin rash begins 3-30 days after the tick bite; however, as many as 18% of patients can present without the skin rash.
  • Stage 2 follows weeks to months later. These patients may develop neurologic (15%), cardiac (5%), or arthritic (60%) manifestations. Neurologic signs can include cranial neuropathy (especially Bell palsy), meningitis, headache, or neuritis.
  • In Stage 3, the most common manifestation is chronic Lyme arthritis. Chronic neurologic syndromes include neuropsychiatric disease and peripheral neuropathy.

Physical

• Ocular manifestations of Lyme disease may involve any portion of the eye and vary depending on the stage of the disease.
• • In stage 1 Lyme disease, the ocular manifestations are conjunctivitis and photophobia. These symptoms are mild and transient, and ophthalmologists usually are not consulted.
  • During stage 2 Lyme disease, significant ophthalmic complications first appear. The most common are various neuro-ophthalmologic signs. Typically, the patient may first present with cranial nerve VII palsy (Bell palsy). Some patients may present with the triad of Lyme neuroborreliosis consisting of cranial nerve palsy, meningitis, and radiculopathy. Blurred vision also can be noted during this stage, secondary to papilledema, optic atrophy, optic or retrobulbar neuritis, or pseudotumor cerebri. Optic nerve disease may be unilateral or bilateral and solitary or associated with other neurologic or neuro-ophthalmologic manifestations. Some evidence exists that children are more predisposed to optic nerve disease than adults.
  • In late stage 2 or stage 3 Lyme disease, most of the severe ocular manifestations of the disease are seen. These include episcleritis, symblepharon, keratitis, iritis, posterior or intermediate uveitis, pars planitis, vitreitis, chorioretinitis, exudative retinal detachment, retinal pigment epithelial detachment, cystoid macular edema, branch artery occlusion, retinal vasculitis, and cranial nerve palsies. Of this group, keratitis, vitreitis, and pars planitis are the most common. The keratitis usually is a bilateral, patchy, nummular stromal keratitis. Posterior segment inflammatory disease generally presents as a bilateral pars planitis associated with granulomatous iritis and vitreitis. Many of these patients also have granulomatous keratic precipitates and posterior synechiae.

Causes

Lyme disease is caused by the spirochete B burgdorferi.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Juvenile rheumatoid arthritis

WORKUP

Section 5 of 10  

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

Lab Studies

• Because many patients with suspected Lyme disease do not recall the tick bite or skin rash, laboratory tests are important in establishing the diagnosis. However, much confusion can occur in the interpretation of the tests used for Lyme disease.
• • The organism and its DNA can be detected in cerebrospinal fluid (CSF), urine, and sera but only early in the disease. Polymerase chain reaction (PCR) is superior to culture, but it is not standardized and not widely available.
  • The two most frequently used tests are the immunofluorescent assay (IFA) and the enzyme-linked immunosorbent assay (ELISA). The principal limitation of these serologic tests has been the high frequency of both false-negative results and false-positive results. False-negative results occur during the acute phase of Lyme disease before patients have developed a sufficient antibody response to give a positive serologic test. False-positive results are due to serologic cross-reactivity among Lyme disease, syphilis, Rocky Mountain spotted fever, and other disorders.
  • To improve diagnostic ability, some laboratories use the immunoblot (Western blot) test. This test is more specific, sensitive, and reliable than the ELISA.
  • The National Conference on Lyme disease recommends a 2-step protocol for disease testing. The first step is to use either Lyme IFA or Lyme ELISA. A Venereal Disease Research Laboratory (VDRL) test and a fluorescent treponemal antibody-absorption (FTA-ABS) test should be completed at the same time. Any positive or equivocal test mandates that immunoglobulin G (IgG) and immunoglobulin M (IgM) immunoblots be performed.

TREATMENT

Section 6 of 10  

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

Medical Care

All patients with stage I Lyme disease should be treated with any one of the following oral antibiotics for 2-3 weeks: tetracycline 500 mg 4 times a day, doxycycline 100 mg 2 times a day, phenoxymethyl penicillin 500 mg 4 times a day, or amoxicillin 500 mg 3-4 times a day.

Children, pregnant women, patients who cannot tolerate tetracycline, and patients who are allergic to penicillin may be given erythromycin 500 mg 4 times a day.

The later stages of Lyme disease can be treated with oral antibiotics, but these patients usually need 30 days of therapy. Patients with severe disease (eg, meningitis, neuroborreliosis, carditis) require parenteral therapy with beta-lactam antibiotics, such as 14-21 days of one of the following: intravenous penicillin G 3-4 million units every 4 hours, intravenous ceftriaxone 2 g/d in divided doses, parenteral penicillin and ceftriaxone in combination, or roxithromycin and cotrimoxazole in combination.

Combination therapy may be worthwhile in patients who do not respond to monotherapy. Physicians should observe patients closely for possible Jarisch-Herxheimer reactions after the institution of therapy; this allergic/inflammatory response may manifest in the skin, mucous membranes, viscera, or nervous system.

Stage I conjunctivitis and photophobia require no therapy. Stage 2 Bell palsy is self-limited but requires supportive therapy to prevent the complications of exposure keratitis. Keratitis and episcleritis benefit from topical corticosteroids, usually a short course of prednisolone acetate 1% or fluorometholone 0.1%.

A treatment regimen for severe neuro-ophthalmic disease (involving the optic nerve) or posterior segment disease (eg, pars planitis, vitreitis) has not been established. Oral corticosteroids without concomitant antibiotics should not be used. The best approach for these patients might be a therapeutic antibiotic trial, in which patients can receive 2-3 weeks of intravenous penicillin or ceftriaxone. If patients respond to treatment, the trial is successful, ocular Lyme disease is diagnosed, and no further therapy is needed. Recurrences of Lyme uveitis, once adequate intravenous therapy has been given, can be treated with judicious corticosteroids.

MEDICATION

Section 7 of 10  

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

The goal of pharmacotherapy is to prevent complications, to reduce morbidity, and to eradicate the infection.

Drug Category: Antibiotics

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

Drug Name	Doxycycline (Bio-Tab, Doryx, Vibramycin, Doxy, Vibra-Tabs)
Description	Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose	Early: 100 mg PO bid for 2-3 wk Late: 100 mg PO bid for 30 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Penicillin V potassium (Veetids, Robicillin VK, V-Cillin K)
Description	Inhibits the biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached, and most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects.
Adult Dose	Early: 500 mg PO qid for 2-3 wk Late: 500 mg PO qid for 30 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing a decrease in the effectiveness of penicillins when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal impairment

Drug Name	Amoxicillin (Trimox, Amoxil, Biomox)
Description	Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria.
Adult Dose	Early: 500 mg PO tid/qid for 2-3 wk Late: 500 mg PO tid/qid for 30 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Reduces efficacy of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Erythromycin (EES, E-Mycin, Eryc, Erythrocin, Ery-Tab)
Description	Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, one half total daily dose may be taken q12h. For more severe infections, double the dose. Primarily used when patient is allergic to penicillin.
Adult Dose	Early: 500 mg PO qid for 2-3 wk Late: 500 mg PO qid for 30 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin, increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Penicillin G (Pfizerpen)
Description	Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Reserved as a parenteral agent in severe cases of the later stages of Lyme disease.
Adult Dose	3-4 million U IV qid for 14 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in impaired renal function

Drug Name	Ceftriaxone (Rocephin)
Description	Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. Reserved for use in severe cases of the later stages of Lyme disease. Can be combined with IV penicillin in patients that do not respond to monotherapy.
Adult Dose	2 g/d IV in divided doses for 14 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in women who are breastfeeding and allergic to penicillin

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Name	Fluorometholone 0.1% (Flarex, Fluor-Op, FML, FML-Forte)
Description	Suppresses migration of polymorphonuclear leukocytes and reverses capillary permeability.
Adult Dose	Ointment: Apply q4h in severe cases; qd/tid in mild-to-moderate cases Solution: 1-2 gtt into conjunctival sac q1h during day; q2h at night until favorable response obtained, then 1 gtt q4h
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity; herpes simplex, keratitis, viral and fungal diseases of the ocular structure
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Prolonged use may result in elevated intraocular pressure or glaucoma

FOLLOW-UP

Section 8 of 10  

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

Deterrence/Prevention

• Preventive measures for Lyme disease rely on personal protection. People in endemic areas should wear long pants and light-colored clothing and use insect repellents whenever venturing into the wooded areas preferred by the Ixodes tick.
• In December 1998, the Food and Drug Administration (FDA) approved the use of the vaccine, LYMERix (Smith-Kline-Beecham), to prevent Lyme disease. However, because of poor demand for the product, the sale was later discontinued in the United States (2002).
• • The vaccine is considered a supplement and not a replacement for standard precautions against Lyme disease. The best way to prevent Lyme disease is for individuals to take preventive measures against tick bites. They should wear long pants and light-colored clothing that they inspect before removal, use appropriate landscape measures around homes, and use insect repellants. However, for patients who live in endemic areas of Lyme disease and who will be outdoors, the vaccine may be advisable.
  • The vaccine is a recombinant outer-surface protein A (rOspA) of B burgdorferi, the bacteria that causes Lyme disease. It induces antibodies that prevent the bacteria from causing illness in vaccinated individuals. However, use of the vaccine presents certain difficulties. The vaccine is approved only for people aged 15-70 years. It is not approved for children, elderly individuals, pregnant woman, or people with chronic joint or neurologic Lyme disease. Also, for maximum protection, at least 3 dosages are required over 1 year. The first dose at 0 time, the next dose at 1 month, and the last dose at 12 months. Finally, the vaccine is not expected to give immunity. Patients require periodic boosters. Current evidence indicates that even in the best case scenario the vaccine has an efficacy of about 80%. Therefore, it is only indicated for patients at high risk.
  • Other problems with the use of the vaccine are that it does not protect against other diseases carried by the deer tick such as ehrlichiosis and babesiosis. The vaccine costs approximately $100 per individual per year, and some insurance companies may not cover the vaccine. The duration of protection is unknown; also the long-term safety of the vaccine has not been determined. Finally, patients should be warned that they probably will develop some local adverse affects, including swelling, pain, and inflammation in the area of the vaccine.

Complications

• Complications depend on the severity of the disease.

Prognosis

• With early detection and treatment, prognosis is favorable.

Patient Education

• For excellent patient education resources, visit eMedicine's Bites and Stings Center and Arthritis Center. Also, see eMedicine's patient education articles Lyme Disease and Ticks.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Because Lyme disease is a disease with varied and complex (and confusing) manifestations, it can be difficult to diagnose. There often are problems with the initial diagnosis, and there can be delays in diagnosis; also, there can be a tendency to overdiagnose the disease, especially in patients with a lifestyle that puts them in a high-risk category. The best way to avoid these problems is to follow the Centers for Disease Control and Prevention (CDC) guidelines regarding diagnosis and to obtain the assistance of an infectious disease expert when one has any questions. Also, be careful as to how the laboratory tests are interpreted, and be sure that they are obtained from a reputable laboratory with experience in testing for Lyme disease.
• Difficulties can arise in choosing the appropriate antibiotic treatment regimen especially in children or potentially pregnant women. Again, an infectious disease consult is helpful in these situations.
• Finally, if one decides to become actively involved in the management of these patients stay abreast of the literature especially in the rapidly changing areas of diagnosis and treatment.

Special Concerns

• See Deterrence/Prevention.

REFERENCES

Section 10 of 10

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

• Bergloff J, Gasser R, Feigl B. Ophthalmic manifestations in Lyme borreliosis. A review. J Neuroophthalmol. Mar 1994;14(1):15-20. [Medline].
• Johnson BJ, Robbins KE, Bailey RE, et al. Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting. J Infect Dis. Aug 1996;174(2):346-53. [Medline].
• Karma A, Seppala I, Mikkila H, et al. Diagnosis and clinical characteristics of ocular Lyme borreliosis. Am J Ophthalmol. Feb 1995;119(2):127-35. [Medline].
• Lesser RL. Ocular manifestations of Lyme disease. Am J Med. Apr 24 1995;98(4A):60S-62S. [Medline].
• Lesser RL, Kornmehl EW, Pachner AR, et al. Neuro-ophthalmologic manifestations of Lyme disease. Ophthalmology. Jun 1990;97(6):699-706. [Medline].
• Magnarelli LA. Current status of laboratory diagnosis for Lyme disease. Am J Med. Apr 24 1995;98(4A):10S-12S; discussion 12S-14S. [Medline].
• Mikkila HO, Seppala IJT, Viljanen MK, et al. The expanding clinical spectrum of ocular Lyme borreliosis. Ophthalmology. Mar 2000;107(3):581-7. [Medline].
• Nadelman RB, Wormser GP. A clinical approach to Lyme disease. Mt Sinai J Med. May 1990;57(3):144-56. [Medline].
• Rothermel H, Hedges TR, Steere AC. Optic neuropathy in children with Lyme disease. Pediatrics. Aug 2001;108(2):477-81. [Medline].
• Steere AC. Lyme disease. N Engl J Med. Aug 31 1989;321(9):586-96. [Medline].
• Steere AC. Lyme disease. N Engl J Med. Jul 12 2001;345(2):115-25. [Medline].
• Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med. Jun 12 2003;348(24):2472-4. [Medline].
• Winward KE, Smith JL, Culbertson WW, Paris-Hamelin A. Ocular Lyme borreliosis. Am J Ophthalmol. Dec 15 1989;108(6):651-7. [Medline].
• Wormser GP. Prospects for a vaccine to prevent Lyme disease in humans. Clin Infect Dis. Nov 1995;21(5):1267-74. [Medline].

Article Last Updated: Nov 1, 2005