Guidelines Summary
The Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology (IDSA/AAN/ACR) have published updated guidelines for the prevention, diagnosis, and treatment of Lyme disease. [6]
Diagnosis and prophylaxis
IDSA/AAN/ACR recommendations regarding diagnosis of Lyme disease include the following:
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Submit removed ticks for species identification.
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Do not test removed Ixodes ticks for Borrelia burgdorferi, as the results do not reliably predict the likelihood of clinical infection.
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Do not test asymptomatic patients for exposure to B burgdorferi after an Ixodes species tick bite
Prophylaxis
IDSA/AAN/ACR guidelines recommend limiting the use of prophylactic antibiotic therapy to adults and children within 72 hours of removal of an identified high-risk tick bite. To be considered high risk, a tick bite must meet all of the following 3 criteria:
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The tick bite was from an identified Ixodes spp. vector species.
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The tick bite occurred in a highly endemic area.
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The tick was attached for ≥36 hours.
If a tick bite cannot be classified with a high level of certainty as a high-risk bite, the guidelines recommend a wait-and-watch approach. Antibiotic prophylaxis is not recommended for bites that are equivocal risk or low risk.
The recommended regimen for prophylaxis is a single oral dose of doxycycline, 200 mg for adults and 4.4 mg/kg (up to a maximum dose of 200 mg) for children.
Erythema migrans
In patients with potential tick exposure in a Lyme disease endemic area who have 1 or more skin lesions compatible with erythema migrans, the IDSA/AAN/ACR guidelines recommend clinical diagnosis rather than laboratory testing. For lesion(s) suggestive of, but atypical for, erythema migrans, the guidelines suggest antibody testing performed on an acute-phase serum sample rather than currently available direct detection methods such as polymerase chain reaction (PCR) or culture performed on blood or skin samples.
If the initial test result is negative, convalescent-phase serum testing may be considered, with the serum sample collected at least 2–3 weeks after collection of the acute-phase serum sample.
Recommended oral antibiotic regimens for treatment of patients with erythema migrans are as follows:
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Doxycyline for 10 days
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Amoxicillin for 14 days
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Cefuroxime axetil for 14 days
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Azithromycin (for patients unable to take doxycycline or beta-lactam antibiotics) for 5–10 days, with a 7-day course preferred in the United States
For patients who develop southern tick–associated rash illness (STARI)—an erythema migrans–like skin lesion following the bite of the lone star tick (Amblyomma americanum)—the guidelines make no recommendation for or against the use of antibiotics.
Testing for Lyme neuroborreliosis
When assessing patients for possible Lyme neuroborreliosis involving either the peripheral nervous system (PNS) or central nervous system (CNS), use serum antibody testing rather than PCR or culture of either cerebrospinal fluid (CSF). For suspected Lyme neuroborreliosis involving the central nervous system, obtain simultaneous samples of CSF and serum for determination of the CSF:serum antibody index, performed by a laboratory using validated methodology.
The guidelines recommend testing for Lyme disease in patients with 1 or more of the following acute neurologic presentations who have epidemiologically plausible exposure to ticks infected with B burgdorferi:
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Meningitis
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Painful radiculoneuritis
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Mononeuropathy multiplex, including confluent mononeuropathy multiplex
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Acute cranial neuropathies (particularly VII and VIII; less commonly III, V, VI, and others)
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Evidence of spinal cord inflammation, particularly in association with painful radiculitis involving related spinal cord segments
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Evidence of inflammation (rare)
The guidelines recommend against Lyme disease testing in patients with any of the following:
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Other neurologic syndromes
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Absence of a history providing other clinical or epidemiologic support for the diagnosis of Lyme disease
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Typical amyotrophic lateral sclerosis
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Relapsing-remitting multiple sclerosis
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Parkinson disease
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Dementia or cognitive decline
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New-onset seizures
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Nonspecific MRI white matter abnormalities confined to the brain in the absence of a history of other clinical or epidemiologic support for the diagnosis of Lyme disease
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Psychiatric illness (in adults)
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Developmental, behavioral, or psychiatric disorders (in children)
Treatment of neuroborreliosis
Recommended antibiotic regimens for Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or with other PNS manifestations are 14-21 days of one of the following:
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Intravenous (IV) ceftriaxone
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IV cefotaxime
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IV penicillin G
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Oral doxycycline
The guidelines recommend using IV over oral antibiotics in patients with Lyme disease–associated parenchymal involvement of the brain or spinal cord.
Lyme carditis
The IDSA/AAN/ACR guidelines include the following suggestions and recommendations regarding Lyme carditis:
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An electrocardiogram (ECG) is suggested in patients with signs or symptoms consistent with Lyme carditis (eg, dyspnea, edema, palpitations, lightheadedness, chest pain, syncope).
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Hospital admission with continuous ECG monitoring is recommended in patients with, or at risk of, severe cardiac complications of Lyme disease (eg, PR prolongation > 300 milliseconds, other arrhythmias, clinical manifestations of myopericarditis).
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Testing for Lyme disease is recommended in patients with acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.
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The guidelines suggest against routine testing for Lyme disease in patients with chronic cardiomyopathy of unknown cause.
Lyme carditis treatment:
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Temporary pacing modalities rather than implantion of a permanent pacemaker is recommended for patients with symptomatic bradycardia due to Lyme carditis that cannot be managed medically.
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For outpatients with Lyme carditis, oral rather than IV antibiotics are suggested.
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For hospitalized patients with Lyme carditis, the suggested strategy is to administer IV ceftriaxone until clinical improvement occurs, then switch to oral antibiotics to complete 14-21 days of treatment. Oral antibiotics recommended for Lyme carditis are doxycycline, amoxicillin, cefuroxime axetil, and azithromycin.
Lyme arthritis
The IDSA/AAN/ACR guidelines include the following suggestions and recommendations regarding Lyme arthritis:
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For diagnosis of Lyme arthritis, serum antibody testing is strongly recommended over PCR or culture of blood or synovial fluid/tissue.
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If more definitive information is required to guide treatment decisions in seropositive patients with possible Lyme arthritis, PCR (rather than Borrelia culture) of synovial fluid or tissue is recommended.
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Oral antibiotic therapy for 28 days is recommended for treatment of Lyme arthritis.
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In patients whose Lyme arthritis shows a partial response (mild residual joint swelling) to a first course of oral antibiotic, the guidelines make no recommendation for or against a second course of antibiotics versus observation.
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In patients whose Lyme arthritis shows no or minimal response (moderate to severe joint swelling with minimal reduction of the joint effusion) to a first course of oral antibiotics, a 2- to 4-week course of IV ceftriaxone is suggested over a second course of oral antibiotics.
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For postantibiotic Lyme arthritis (ie, after failure of 1 course of oral antibiotics and 1 course of IV antibiotics), the guidelines suggest referral to a rheumatologist or other trained specialist for consideration of the use of disease-modifying antirheumatic drugs (DMARDs), biologic agents, intra-articular steroids, or arthroscopic synovectomy. Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included 1 course of IV therapy.
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Lyme disease. The bacterium Borrelia burgdorferi (darkfield microscopy technique, 400X; courtesy of the US Centers for Disease Control and Prevention).
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Lyme disease. Magnified ticks at various stages of development.
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Ticks are the most common vectors for vector-borne diseases in the United States. In North America, tick bites can cause Lyme disease, human granulocytic and monocytic ehrlichiosis, babesiosis, relapsing fever, Rocky Mountain spotted fever, Colorado tick fever, tularemia, Q fever, and tick paralysis. Europe has a similar list of illnesses caused by ticks, but additional concerns include boutonneuse fever and tick-borne encephalitis. Lyme disease is one of the most prominent tick-borne diseases, and its main vector is the tick genus Ixodes, primarily Ixodes scapularis. Image courtesy of the US Centers of Disease Control and Prevention.
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Lyme disease. Approximate US distribution of Ixodes scapularis. Image courtesy of the US Centers for Disease Control and Prevention.
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Lyme disease. In general, Ixodes scapularis must be attached for at least 24 hours to transmit the spirochete to the host mammal. Prophylactic antibiotics are more likely to be helpful if feeding is longer. This photo shows 2 I scapularis nymphs. The one on the right is unfed; the other has been feeding for 48 hours. Note its larger size and the fact that the midgut diverticula (delicate brown linear areas on the body) are blurred. Photo by Darlyne Murawski; reproduced with permission.
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Lyme disease. Normal and engorged Ixodes ticks.
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Amblyomma americanum is the tick vector for monocytic ehrlichiosis and tularemia. An adult and a nymphal form are shown (common match shown for size comparison). Image by Darlyne Murawski; reproduced with permission.
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Approximate US distribution of Amblyomma americanum. Image courtesy of the US Centers for Disease Control and Prevention.
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The soft-bodied tick of the genus Ornithodoros transmits various Borrelia species that cause relapsing fever. Photo courtesy of Julie Rawlings, MPH, Texas Department of Health. Relapsing fever is characterized by recurrent acute episodes of fever (usually >39°C). It is a vector-borne illness spread by lice and ticks. The spirochete species Borrelia is responsible.
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The Ixodes scapularis tick is considerably smaller than the Dermacentor tick. The former is the vector for Lyme disease, granulocytic ehrlichiosis, and babesiosis. The latter is the vector for Rocky Mountain spotted fever. This photo displays an adult I scapularis tick (on the right) next to an adult Dermacentor variabilis; both are next to a common match displayed for scale. Photo by Darlyne Murawski; reproduced with permission.
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Approximate US distribution of Dermacentor andersoni. Image courtesy of the US Centers for Disease Control and Prevention.
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Rhipicephalus ticks are vectors for babesiosis and rickettsial infections, among others. Image courtesy of Dirk M. Elston, MD. In typical practice, testing ticks for tick-borne infectious organisms is not generally recommended. However, healthcare practitioners should become familiar with the clinical manifestations of tick-borne diseases (eg, Lyme disease, especially those practicing in endemic areas) and maintain a high index of suspicion during warmer months. Ticks can be placed in a sealed container with alcohol if they need to be transported and identified.
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To remove a tick, use fine-tipped forceps and wear gloves. Grasp the tick as close to the skin surface as possible, including the mouth parts, and pull upward with steady, even traction. Do not twist or jerk the tick because this may cause the mouth parts to break off and remain in the skin; however, note that the mouth parts themselves are not infectious. When removing, wear gloves to avoid possible infection.
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Lyme disease. This patient's erythema migrans rash demonstrates several key features of the rash, including size, location, and presence of a central punctum, which can be seen right at the lateral margin of the inferior gluteal fold. Note that the color is uniform; this pattern probably is more common than the classic pattern of central clearing. On history, this patient was found to live in an endemic area for ticks and to pull ticks off her dog daily.
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Erythema migrans, the characteristic rash of early Lyme disease.
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Lyme disease. The thorax and torso are typical locations for erythema migrans. The lesion is slightly darker in the center, a common variation. In addition, this patient worked outdoors in a highly endemic area. Physical examination also revealed a right axillary lymph node.
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Lyme disease. Photo of the left side of the neck of a patient who had pulled a tick from this region 7 days previously. Note the raised vesicular center, which is a variant of erythema migrans. The patient had a Jarisch-Herxheimer reaction approximately 18 hours after the first dose of doxycycline.
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Lyme disease. Classic target lesion with concentric rings of erythema, which often show central clearing. Although this morphology was emphasized in earlier North American literature, it only represents approximately 40% of erythema migrans lesions in the United States. This pattern is more common in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn.
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Typical appearance of erythema migrans, the bull's-eye rash of Lyme disease.
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Lyme disease. Bulls-eye rash.
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Lyme disease. Photo of erythema migrans on the right thigh of a toddler. The size and location are typical of erythema migrans, as is the history of the patient vacationing on Fire Island, NY, in the month of August. No tick bite had been noted at this location. Approximately 25% of patients with Lyme disease are children, which is the same percentage of patients who do not recall a tick bite. Courtesy of Dr John Hanrahan.
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Lyme disease. Multiple lesions of erythema migrans occur in approximately 20% of patients. A carpenter from Nantucket who worked predominantly outside had been treated with clotrimazole/betamethasone for 1 week for a presumed tineal infection, but the initial lesion grew, and new ones developed. He then presented to the emergency department with the rashes seen in this photo. The patient had no fever and only mild systemic symptoms. He was treated with a 3-week course of oral antibiotics.
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Lyme disease. The rash on the ankle seen in this photo is consistent with both cellulitis (deep red hue, acral location, mild tenderness) and erythema migrans (presentation in July, in an area highly endemic for Lyme disease). In this situation, treatment with a drug that covers both diseases (eg, cefuroxime or amoxicillin-clavulanate) is an effective strategy.
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Lyme disease. Borrelial lymphocytoma of the earlobe, which shows a bluish red discoloration. The location is typical in children, as opposed to the nipple in adults. This manifestation of Lyme disease is uncommon and occurs only in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn.
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A rarely reported noninfectious complication for tick bites is alopecia. It can begin within a week of tick removal and typically occurs in a 3- to 4-cm circle around a tick bite on the scalp. A moth-eaten alopecia of the scalp caused by bites of Dermacentor variabilis (the American dog tick) has also been described. No particular species appears more likely to cause alopecia. Hair regrowth typically occurs within 1-3 months, although permanent alopecia has been observed.
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Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic phase. As the term suggests, the lesion occurs acrally and ultimately results in skin described as being like cigarette paper. Courtesy of Lyme Disease Foundation, Hartford, Conn.
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Blood smear showing likely babesiosis. Babesiosis can be difficult to distinguish from malaria on a blood smear.
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Life cycle of the Ixodes dammini tick. Courtesy of Elsevier.
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Lyme disease in the United States is concentrated heavily in the northeast and upper Midwest; it does not occur nationwide. Dots on the map indicate the infected person's county of residence, not the place where they were infected. Courtesy of the US Centers for Disease Control and Prevention (CDC).
Tables
- Table 1. Clinical presentation and therapy for the stages of Lyme disease
- Table 2. Adult and pediatric treatment options, dosages, and routes of administration
- Table 3. Comparison of Infectious Diseases Society of America (IDSA) and International Lyme and Associated Diseases Society (ILADS) recommendations for Lyme disease treatment
Disease Stage |
Clinical Manifestations |
Treatment |
Duration |
Early localized |
Erythema migrans |
Oral |
Doxycycline, 10 days Amoxicillin or cefuroxime axetil, 14 days Azithromycin, 7 days |
Early disseminated |
Multiple erythema migrans |
Oral |
14 days |
Isolated cranial nerve palsy |
Oral |
14-21 days |
|
Meningoradiculoneuritis |
Oral |
14-28 days |
|
Meningitis |
Intravenous or oral |
14-21 days |
|
Carditis |
|
|
|
-Ambulatory |
Oral |
14-21 days |
|
-Hospitalized |
Intravenous followed by oral |
14-21 days |
|
Borrelial lymphocytoma |
Oral |
14 days |
|
Late |
Arthritis |
Oral |
28 days |
Recurrent arthritis after oral therapy |
Oral or intravenous |
28 days or 14-28 days |
|
Encephalitis |
Intravenous |
14-28 days |
|
Acrodermatitis chronica atrophicans |
Oral |
21-28 days |
|
Treatment |
Adult Dose |
Pediatric Dose |
Oral Therapy |
Doxycycline (patients > 8 y) |
100 mg twice a day |
4 mg/kg (up to 100 mg) twice a day |
Amoxicillin |
500 mg three times a day |
50 mg/kg/day (up to 500 mg) in three divided doses |
|
Cefuroxime axetil |
500 mg twice a day |
30 mg/kg/day (up to 500 mg) in two divided doses |
|
Phenoxymethylpenicillin |
500 mg four times a day, or 1 gm three times a day |
50-100 mg/kg/day in three divided doses; maximum 1 g/dose |
|
Azithromycin (for patients unable to take doxycycline or beta-lactams) |
500 mg once a day
|
50-100 mg/kg/day in three divided doses; maximum 1 g/dose |
|
Intravenous therapy |
Ceftriaxone |
2 g once a day |
10 mg/kg/day (maximum, 500 mg/day) |
Cefotaxime |
2 g every 8 h |
150-200 mg/kg (up to 2 g) every 8 h |
|
Penicillin G |
18-24 million U/d divided every 4 h |
200,000-400,000 mg/kg (up to 2 g) every 8 h |
Treatment Focus |
IDSA |
ILADS |
Treatment of a tick bite without symptoms of Lyme disease |
Doxycycline, 200 mg as a single dose |
Doxycycline, 100 mg bid for 20 days |
Erythema migrans |
Doxycycline, amoxicillin, or cefuroxime for 14-21 days |
Doxycycline, amoxicillin, or cefuroxime for 28-42 days or azithromycin for at least 21 days |
“Persisting symptoms of Lyme disease” |
No antibiotic therapy |
Multiple agents (individually or in combination) are mentioned without specific doses or duration recommended |
