Little Tick Bite, Big Problem: Lyme Disease Materials

LITTLE TICK BITE, BIG PROBLEM: LYME DISEASE

Faculty:

Jeanette Y. Wick, RPh, MBA, FASCP

Jeannette Y. Wick is the Director of the Office of Pharmacy Professional Development at the University of Connecticut.

Pamela Sardo, PharmD, BS

Pamela Sardo, PharmD, BS, is a freelance medical writer and licensed pharmacist. She is the founder and principal at Sardo Solutions in Texas. Pam received her BS from the University of Connecticut and her PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, and managed health care responsibilities across a broad range of therapeutic classes and disease states.

Abstract

Lyme disease is the most common vector-borne disease and the sixth most common notifiable infectious disease in the United States. Lyme disease is a vector-borne zoonotic disease usually transmitted by Borrelia burgdorferi via ticks of the genus Ixodes. Generally associated with a tick bite lasting 36 hours or more and closely linked to erythema migrans, this infectious disease is rarely fatal but often causes symptoms such as arthralgias, arthritis, central nervous system complications, and other problems. The Centers for Disease Control and Prevention and numerous professional organizations have developed guidelines for prophylaxis and treatment. Ample information is available to help individuals who wish to avoid tick bites, successfully remove ticks, access testing, or receive treatment. Pharmacy staff are apt to encounter many of these individuals and can be excellent healthcare resources.

Accreditation Statements

In support of improving patient care, RxCe.com LLC is jointly accredited by the Accreditation Council^TM for Continuing Medical Education (ACCME^®), the Accreditation Council for Pharmacy Education (ACPE^®), and the American Nurses Credentialing Center (ANCC^®), to provide continuing education for the healthcare team.

Joint Universal Activity Number: The Joint Accreditation Universal Activity Numbers assigned to this activity are as follows:

Pharmacists: JA4008424-0000-26-124-H01-P

Pharmacy Technicians: JA4008424-0000-26-124-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.

Credit Types:

Pharmacy - 2 Credits

Type of Activity: Knowledge

Media: Computer-Based Training (i.e., online courses)

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Activity Pre-Test, Post-Test, and Activity Evaluation.

Release Date: June 29, 2026 Expiration Date: March 12, 2027

Target Audience: This educational activity is for Pharmacists and Pharmacy Technicians

How to Earn Credit: From June 29, 2026, through March 12, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Take the “Educational Activity Pre-Test;”

Study the section entitled “Educational Activity;” and

Complete the Educational Activity Post-Test and Activity Evaluation. The Educational Activity Post-Test will be graded automatically. Following successful completion of the Educational Activity Post-Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

CE and CME Credits: Credits for this course will be uploaded to CPE Monitor^® for pharmacists and pharmacy technicians.

Statement of Need

Lyme disease is a vector-borne, zoonotic infection caused by two species of the bacterium spirochete Borrelia. Healthcare clinicians in states where tick-borne illnesses are prevalent, as well as in states or regions that may not usually see these illnesses, need to be skilled in identifying and treating Lyme disease. This course provides education on these clinical skills.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

List the prevalence of and risk factors for Lyme disease

Recognize Lyme disease’s signs, symptoms, and more serious manifestations

Describe prophylaxis and treatment options in Lyme disease’s various stages

Use good patient engagement techniques to ensure optimal outcomes in patients who suspect they have Lyme disease

Disclosures

The following individuals were involved in planning, developing, and/or authoring this activity: Jeannette Y. Wick, RPh, MBA, FASCP; and Pamela Sardo, PharmD, BS. None of the individuals involved in developing this activity has a conflict of interest or financial relationships related to the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity. 

© RxCe.com LLC 2026: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity Pre-Test

Which of the following individuals is at the highest risk of developing Lyme disease pursuant to a tick bite?

A 72-year-old woman who lives on the island of Oahu in Hawaii and plays mahjong daily indoors

A 36-year-old man who lives in the desert area of Nevada and enjoys horseback riding

An 8-year-old child who lives in a rural community in the Northeast and plays outside often

A 10-year-old child who lives in Phoenix, AZ, with hobbies that include playing the piano and competing in spelling bees

A patient indicates he was recently diagnosed with Lyme disease. He indicates that he has developed facial paralysis and some tingling or numbness in his extremities. What might this be?

Acrodermatitis chronica atrophicans

Borrelial lymphocytoma

erythema migrans

neuroborreliosis

A patient who is familiar to you comes to the pharmacy and says that she has been diagnosed with Lyme disease. You notice dog hair on her clothing, and she confirms she has three dogs. When you ask if her dogs are receiving effective tick prevention, she replies, “Yes, during the high-risk months.” Which of the following statements best describes an appropriate response?

You really need to use tick prevention year-round.

If that's what your veterinarian recommended, good.

The high-risk months are September through March.

There's no need to say anything about this situation.

Educational Activity

Little Tick Bite, Big Problem: Lyme Disease

Introduction

Lyme disease has been around for centuries, but it was not identified as a disease until the 1970s. Lyme disease is caused by a bacterium belonging to the genus Borrelia. It appears primarily in the eastern half of the continental United States (U.S.) but continues to migrate westward into other parts of the country. While healthcare clinicians in states where tick-borne illnesses are prevalent need to be skilled in identifying and treating Lyme disease, clinicians in states or regions that may not see tick-borne illnesses should also be prepared because of the westward migration of ticks. Guidelines for the prophylaxis and treatment of Lyme disease are available, along with ample information to help individuals avoid tick bites, successfully remove ticks, access testing, or receive treatment. This continuing education activity will discuss some of the disease’s history and highlight prevention, prophylaxis, and treatment options.

Lyme Disease and Ticks

Lyme disease is a vector-borne, zoonotic infection caused by two species of the bacterium spirochete Borrelia.¹ Borrelia burgdorferi has traditionally been the primary species of concern and continues to be the most important vector; however, Borrelia mayonii emerged in 2016 as another vector.¹

Infected ticks of the genus Ixodes are the vectors—they carry the disease and transmit it to humans when they bite. Across the U.S., two types of ticks transmit B. burgdorferi to humans: blacklegged ticks (Ixodes scapularis, called deer ticks colloquially) in the New England and Great Lakes areas and, to a much lesser extent, western blacklegged ticks (Ixodes pacificus) in the West.²

Public health officials are concerned that ticks, as vectors for B. burgdorferi, are expanding into new geographic areas, requiring greater public health surveillance.3 For example, in October 2023, a female Ixodes tick was removed from a hunting dog in Bozeman, Montana. The owner and dog had recently spent time in eastern Montana. The tick was identified as Ixodes scapularis based on morphological characteristics and genomic sequencing. Prior to this report, Montana had no reported Ixodes scapularis ticks or their western counterpart, Ixodes pacificus. This means that clinicians in parts of the country that may not see Lyme disease or other tick-borne illnesses should also be knowledgeable in identifying and treating them.

POINT TO PONDER: How many diseases are only discovered after people who live close to each other find they are experiencing similar symptoms?

History of Lyme Disease

Lyme disease was an unnamed culprit until a group of mothers in Connecticut became concerned about clusters of unexplained illnesses in the 1970s. Although knowledge of Lyme disease is relatively new, it has been around for thousands of years.^4-6 An autopsy of a Neolithic mummy, the Iceman named Ötzi, suggested the presence of Lyme disease from a Borrelia burgdorferi infection. This neolithic man died 5,300 years ago on an icy mountain in Europe.^4-6

Today, infectious disease specialists know considerably more about Lyme disease than they did in 1975. In the early 1900s, European physicians noted an erythematous migrating rash, now known as erythema migrans (EM), that occurred after tick bites. In the 1940s, researchers isolated a spirochete-like bacterium associated with skin lesions from EM and linked it to a systemic illness. Subsequently, they found that this tick-borne illness—much like another spirochete-induced illness (syphilis)—was susceptible to penicillin.²

Lyme disease earned its new name and became a growing national concern in 1975.^7-10 Physicians in Lyme and Old Lyme, Connecticut, were baffled by several children in specific neighborhoods who developed an unusual rash and what was assumed to be juvenile rheumatoid arthritis (JRA). It was the children’s mothers who contacted the Connecticut State Health Department, which in turn recruited help from Yale University. Epidemiologic findings indicated that the prevalence of this specific symptom constellation was 4.3/1000 residents and 12.2/1000 children in the area. The “new” disease rate in children was 100 times that of JRA. Clinical and demographic investigation suggested that these children and several adults were suffering from the disease called EM in Europe. In 1977, the research team identified ticks as the most likely vector.^7,9

In 1982, researchers found B. burgdorferi spirochetes related to the illness in the intestinal tract of the adult deer tick Ixodes dammini (now renamed Ixodes scapularis).² The Centers for Disease Control and Prevention (CDC) established a surveillance program and classified Lyme disease as a nationally notifiable disease in 1991.¹¹ Nationally notifiable diseases are those that health providers must report to state or local public health officials when they diagnose them, usually by law. Notifiable diseases are of public interest because they may be contagious, severe, or occur at a high frequency.¹²

Reservoirs and Transmission

In the U.S., the white-footed mouse is the primary animal reservoir (the infectious pathogen’s long-term host) for Lyme disease, and in the northeastern U.S., chipmunks, short-tailed and masked shrews (small mouse-like rodents), and eastern gray squirrels are also reservoirs. Some mammals, including dogs, can develop Lyme disease but do not directly transmit it to humans.¹³ 

Ticks are Lyme disease’s only living agents that carry and transmit this infectious pathogen to other living organisms; they are called vectors.² Ticks are sedentary predators that employ a position known as questing to find prey. They grip leaves, grass, or underbrush using their third and fourth pair of legs, holding their first pair of legs outstretched.^14,15 Hosts that brush against the waiting tick become the tick’s prey.

The Ixodes scapularis tick’s trajectory from birth to death is a short affair, usually spanning two to three years and progressing through egg, larval, nymph, and adult stages.¹⁶ Their survival during the larval and nymph stages requires a new host for a blood meal for growth to the next stage. Adult females need a blood supply to produce eggs. Nymphal and larval forms of the Ixodes tick rely on the white-footed mouse for nourishment, while adult ticks feed on deer. Black-legged ticks can feed on mammals, birds, reptiles, and amphibians. Ticks acquire Borrelia from infected hosts, and an interesting point is that female ticks do not transmit Borrelia to their offspring.¹⁶

Accurately identifying ticks is critical when discussing Lyme disease. Ixodes ticks are much smaller than common dog ticks, with the former about the size of a sesame seed and the latter 5 mm or larger (the size of a pencil top eraser). Larval and nymphal ticks, often implicated in tick bites, are a few millimeters in diameter. Adult ticks are larger. For this reason, experts indicate that people who are bitten and remove a tick properly should save it and submit it to the health department for identification.¹⁷ The SIDEBAR below discusses proper tick removal. For a tick to transmit Borrelia to a human, the spirochetes must migrate from its gut to its salivary glands. That process takes three to four days after a bite in most cases. Removing the tick before then can considerably reduce the chances of Lyme disease.¹⁶

Patients should remove ticks promptly and entirely and only in ways that prevent them from releasing additional saliva or regurgitating their stomach contents into the bite wound.

SIDEBAR: How to Remove Ticks Correctly^16,17

CORRECT: DO THIS

INCORRECT: DO NOT DO THIS

Use an approved tick-removal tool, fine-pointed tweezers, or, if neither of these is available, use fine cotton thread or dental floss Clean the tool with antiseptic Grasp the tick from the head or mouth (not the body) and pull the tick out without twisting If using a thread, tie a single loop around the tick’s mouthparts as close to the skin as possible, then pull upwards and outwards without twisting Cleanse the bite site and the tool after tick removal with antiseptic Place the tick in a sealed container in case a doctor needs to see it Wash hands thoroughly

Squeeze the tick’s body because this may cause the head and body to separate, leaving the head in the skin Use your fingernails to remove a tick because an infection can occur through any breaks in the skin Crush the tick’s body because it may regurgitate its infected stomach contents into the bite wound Apply anything to kill the tick because any discomfort can cause the tick to regurgitate or release saliva

Epidemiology and Burden of Disease

Lyme disease is the most common vector-borne disease, and the sixth most common notifiable infectious disease in the U.S.¹⁸ Local and state health departments are responsible for reporting Lyme disease cases.¹⁹ Once local and state health departments receive word of possible Lyme disease cases, they investigate them to classify them according to the national surveillance “case definition.”¹⁹ Confirmed or probable cases of Lyme disease are reported to the CDC through the National Notifiable Disease Surveillance System (NNDSS). The case definition defines the disease for public health surveillance. It is not intended to be used for making a clinical diagnosis or determining treatment.¹⁹

A 2021 study estimated that the number of Lyme disease cases in the United States exceeded 400,000 annually.^20,21 Additionally, insurance estimates indicate approximately 476,000 people are diagnosed or treated for Lyme disease annually in the U.S.²² The difference between these numbers is probably because so many people are treated presumptively (based on clinical suspicion).²¹

Against this backdrop, the CDC reported 63,000 confirmed and probable cases of Lyme disease in 2021.²² In previous years, the CDC reported 30,000 cases. However, the CDC revised the “case definition” of Lyme disease in 2022 and applied the new definition to cases from 2021.¹⁹ The revised case definition allows case reporting from high-incidence jurisdictions to be based solely on laboratory evidence, removing the need for supporting clinical information. Cases reported from low-incidence jurisdictions continue to require laboratory evidence and supporting clinical information.¹⁸ In the end, the discrepancy between the expert estimates and the CDC’s numbers speaks to the issue of possible underreporting.²¹

National Notifiable Disease Surveillance System data indicates that the number of areas associated with a high incidence of Lyme disease is growing; the number of counties with an incidence of 10 or more confirmed cases per 100,000 residents increased from 324 in 2008 to 432 in 2019.^18,23 People who live in the Northeast, mid-Atlantic, and upper Midwest are at greatest risk, with pockets of elevated risk along the West Coast. Large populations of the Ixodes tick hosts (white-footed mice and white-tailed deer) are directly associated with elevated risk.^2,24

Lyme disease is not just an American concern. A recent meta-analysis indicated that 14.5% of the world’s population may have had Lyme disease. Based on results from 90 studies enrolling more than 158,000 people, seropositivity rates indicated that 20.7% of residents in Central Europe, 15.9% in Eastern Asia, and 13.5% in Western Europe had Lyme disease. The rate in North America was 9%.²⁵

Risk Factors for Lyme Disease

Lyme disease is an indiscriminate infection affecting males and females equally. It is diagnosed most often in children aged 5 to 14 years and adults aged 55 to 70 years.² Factors associated with the increased probability of tick-borne disease are listed below.²⁶ Of the factors listed, pet ownership confers the highest risk.^23,26

deer abundance

gardens

landscapes interspersed with herbaceous and forested habitat

low human population density

outdoor occupational activities, such as outdoor work

participating in recreational outdoor activities such as jogging, walking, off-road cycling, and horseback riding

pet ownership

The issue of deer is interesting. Although settlers in the U.S., overhunted white-tailed deer almost to the point of extinction in the early 1900s, many states now report explosive populations of white deer. The causes of this population explosion are many. Their predators (cougars and wolves) are now rare; deer have found human environments (fields, gardens, lawns, and orchards) attractive and available; and humans have introduced deer to areas that were traditionally deer-free.^27,28 In addition, deer thrive in many environments and reproduce prolifically. Consider this: seven deer introduced onto the 9-square-mile Block Island, Rhode Island, in 1967 reproduced to a number of 700 deer by 1994.^27,28

POINT TO PONDER: What risk factors for tick-borne disease are most prevalent in the area where you live?

Signs and Symptoms of Lyme Disease

Lyme disease’s signs and symptoms progress as the disease advances, and in many cases, symptoms may be atypical, making diagnosis difficult. Its three stages are as follows:

Early localized disease

Early disseminated disease, and

Late disease

Erythema migrans, Lyme disease’s hallmark sign, is found in about 75% to 80% of cases a week or two after a bite (but can appear up to 30 days later).² It first presents one to four weeks after the bite and lasts up to several weeks. The expanding rash often has a bull’s-eye appearance, with a red ring around a clear area and a red center.²⁶ It usually radiates from the tick bite site in a five- or six-inch circle (but can be bigger or smaller) but may occur elsewhere on the body.²⁹ The rash tends to be silent with no pain, pruritus, swelling, heat, or scales, but it can present with these symptoms. It may appear at different sites on the body and enlarge as the infection spreads.³⁰ It lasts for three to five weeks.²⁹ Noting that a significant number of patients do not develop EM, diagnosis can be difficult if patients cannot remember or did not notice a tick bite—a situation that occurs in 30% to 50% of individuals.³¹ For physicians practicing in geographic areas with a high risk of tick bites and infections, diagnosing Lyme disease remains challenging.³² Misdiagnosis or delayed diagnosis is common for this reason.³²

Erythema migrans appears to be more common in the U.S., than in Europe. EM, when present, is associated with more intense inflammation and a systemic spread than in cases where it is absent. Researchers suggest a reason: In the U.S., only one species of B. burgdorferi causes Lyme disease. In Europe, three other species can cause Lyme disease. Another manifestation differs in European patients.³³

Lyme disease is also associated with two other dermatologic conditions:

Borrelial lymphocytoma, which is a red, swollen lump. In children, these tend to appear on the ear. In adults, they sometimes appear on the nipple or scrotum.

Acrodermatitis chronica atrophicans, which manifests as swelling, hardened skin, and deep lines in patients who have had Lyme disease for years

Lyme disease’s early localized stage may include flu-like symptoms, including fever, sweats, chills, malaise, myalgias, arthralgia, headache, and tender local adenopathy. As the disease progresses, additional symptoms may include tender regional adenopathy, conjunctivitis, carditis, and neurologic manifestations such as meningitis (which presents as fever, headache, sensitivity to light, and stiff neck) and peripheral nerve involvement (e.g., radiculoneuropathy [numbness, tingling, “shooting” pain, or weakness in the arms or legs]) or cranial nerve palsy.³⁴

Early Disseminated Disease

Americans often complain of mild to moderate musculoskeletal aches (myalgia) or pains (arthralgia). Oligoarthritis (joint stiffness and swelling in fewer than five joints, most often affecting large joints, such as the knees, elbows, and ankles) is also possible and often confused with JRA.²

In most cases, early dissemination spreads the bacteria into the nervous system, leading to a condition called neuroborreliosis. It occurs earlier in children than adults and may present as meningitis or cranial neuritis. One possible explanation for the difference is that ticks tend to bite children more often on the upper trunk and head, potentially making the CNS more accessible to the spirochete.³⁵ Other symptoms include facial palsy (facial paralysis similar to Bell’s palsy), tingling or numbness in the extremities, enlarged lymph glands, abnormal pulse, sore throat, vision changes, fever (100°F to 102°F), and severe fatigue.^29,36 Other central nervous system conditions occur less frequently.²

Cardiac involvement, which occurs in about 1% of patients, may include atrioventricular blockade, myopericarditis, and cardiomyopathy.^37,38 In children, early dissemination, especially neuroborreliosis, usually occurs earlier than in adults. This might be due to a different site of the tick bite.

Late Disease

In the U.S., the late phase can occur months to years after the bite. It primarily manifests as arthritis in the large joints, especially the knees. Patients with the alloantigen HLA-DR4 have a high risk of developing chronic arthritis.³⁹ Pharmacy staff should note that arthritis differs from arthralgia, which is a simple ache or pain. Warmth, swelling from effusion, and limited range of motion are additional characteristics of arthritis.³⁹

Occasionally, patients develop chronic polyneuropathy or encephalopathy with insomnia, malaise, impaired mentation, and potential personality changes. Untreated Lyme disease can create substantial disability, but it is rarely fatal.²

Diagnosis

When assessing patients for Lyme disease, the CDC recommends healthcare providers use a pre-test probability assessment that includes three questions:⁴⁰

Has the patient been in an area where Lyme disease is common?

Was the patient likely exposed to ticks?

Does the patient have symptoms characteristic of Lyme disease?

If all questions are answered yes, the pretest probability is high, and the prescriber should initiate treatment. Healthcare providers should use their discretion if any question is answered no and order serologic testing if warranted.⁴⁰

The CDC recommends a two-step process that uses the same blood sample to detect antibodies against B. burgdorferi . The first step is an enzyme immunoassay (EIA) or immunofluorescence assay (IFA)–total Lyme titer or immunoglobulin A and immunoglobulin M titers.⁴⁰ The EIA or IFA tests are sensitive but not necessarily specific. If the first step is negative, then no further testing is required. If the results of the first test are positive or indeterminate, the second, more specific Western immunoblot test follows. Positive results on both tests confirm the diagnosis.⁴⁰

The testing procedure is structured this way because these tests are prone to false negatives and false positives. The overall false-positive rate is approximately 5%.² The EIA and IFA tests, which look for antibodies to B. burgdorferi, may be less sensitive early in the disease when antibodies are just developing. Early testing with EIA and IFA may yield false-negative results. Patients with mononucleosis, autoimmune states, or Treponema pallidum infection may experience false-positive results; healthcare providers must consider each patient’s medical history when deciding whether to order testing.² The issue of testing is also more complicated since individuals can now order their own tests from private companies, which is discussed below.

Healthcare teams must also note that Lyme antibodies often persist in the blood for months or years. Clinicians may have difficulty distinguishing active infections from past infections.

In an attempt to streamline diagnosis, the FDA cleared a new testing paradigm in July 2019. In the new process, the laboratory processes two EIAs concurrently or sequentially rather than in the two-step process described above.⁴¹ Clinical tests showed that this alternative approach is as accurate as the two-tiered process.^41,42

In Lyme disease’s late phases, healthcare providers can consider joint aspiration, cerebrospinal fluid analysis, and an electrocardiogram (ECG) to assess the extent of the disease.^19,43 Current Infectious Diseases Society of America (IDSA) guidelines recommend ECG in patients with dyspnea, edema, palpitations, lightheadedness, chest pain, and syncope, which may indicate Lyme carditis.^19,43

Most patients with Lyme disease fully recover with prompt diagnosis and treatment. Untreated Lyme disease can lead to serious health concerns, including arthritis, carditis, and neurologic or ocular manifestations.⁴⁴

Prevention

The FDA approved one manufacturer’s vaccine to protect against Lyme disease (LYMErix) in 1998, but poor uptake prompted the manufacturer to discontinue it in 2002.⁴⁵ The vaccine’s effects were short-lived, so protection has probably waned among patients vaccinated before its discontinuation. Clinicians should manage them as they do patients who never received the vaccine.²⁰ Interest in developing a replacement vaccine appears to be growing in light of the increase in Lyme disease cases.^46,47

Ticks live in grassy, brushy, or wooded areas and on animals. Although they are most active during the warmest months, tick exposure can occur all year.²⁰ The CDC provides excellent and comprehensive information on preventing tick bites, and technicians can ensure printed copies are available and given to patients in high-risk areas. When counseling patients on preventing tick bites, pharmacists should ask about pet ownership and discuss how to prevent ticks on animals.^16,17,20

PREVENTING TICK BITES: The CDC’s Preventing Tick Bites Information can be found on the CDC’s website at the following link: https://www.cdc.gov/ticks/avoid/on_people.html#:~:text=Know%20where%20to%20expect%20ticks.&text=Many%20people%20get%20ticks%20in,remain%20protective%20through%20several%20washings The CDC also has a website specific to hunters: “It’s open season on ticks!” This information can be found on the CDC’s website at the following link: https://www.cdc.gov/ncezid/dvbd/media/hunting-season-ticks.html

Prophylaxis and Treatment

Several groups have published Lyme disease guidelines. The IDSA published a comprehensive guideline on Lyme disease in 2020 jointly with the American Academy of Neurology and the American College of Rheumatology, and its recommendations are very similar to the CDC’s.¹⁹

POINT TO PONDER: How would you differentiate between a patient who may need prophylaxis and one who may need treatment?

Antibiotic Prophylaxis

In areas where tick bites are extremely common, the risk of infection after a prolonged bite is 10% to 25%.^48,49 Prescribers should consider antibiotic prophylaxis for patients within 72 hours of removing a tick after a high-risk bite (e.g., those from an engorged Ixodes tick in a highly endemic area or that have been attached for 36 hours or more), but not after lower-risk bites. Since spirochetes need up to 36 hours after a bite to migrate from the tick gut to the salivary glands, the risk of transmission of B. burgdorferi from an unengorged tick is negligible, and the guidelines recommend using a “watch and wait” approach.^50-52

The guidelines recommend a single dose of 200 mg of doxycycline for adults and 4.4 mg/kg, up to a maximum of 200 mg, for children for prophylaxis.¹⁹ One change that warrants special note is the use of doxycycline in children.⁵³ Doxycycline has traditionally been contraindicated in children aged eight years and younger and pregnant women due to possible staining of primary teeth. These concerns are largely based on findings from studies of tetracycline. More recent research suggests that doxycycline for up to 21 days is safe in young children, and a growing consensus supports its use in children.⁵¹ Data on doxycycline’s safety in breastfeeding women is insufficient, so its use is not currently recommended.

Treatment

Most patients with Lyme disease recover rapidly and completely after treatment. The patient’s clinical manifestations, disease stage, and concomitant medical conditions or allergies drive the choice of antibiotic, route of administration, and duration of therapy for Lyme disease. Table 1 summarizes the guideline treatment recommendations.

Table 1

Guideline Recommended Antibiotic Dosing for Lyme Disease¹⁹

	Antibiotic	Adult Dose	Pediatric Dose	Treatment Duration for Specific Indications
First-line therapy (oral)	doxycycline	100 mg BID or 200 mg once daily	4.4 mg/kg/day in two divided doses up to a maximum of 100 mg BID	10 days for EM 14 to 21 days for neurologic manifestations 14 days for carditis 28 days for arthritis
	amoxicillin	500 mg TID	50 mg/kg/day in three divided doses up to a maximum of 500 mg per dose	14 days for EM 14 days for carditis 28 days for arthritis
	cefuroxime	500 mg BID	30 mg/kg/day and two divided doses up to a maximum of 500 mg per dose	14 days for EM 14 days for carditis
	phenoxymethyl-penicillin	500 mg QID or 1g TID	50 to 100 mg/kg/day divided in three doses up to our maximum of 1g per dose	14 days for EM 14 days for carditis
Second- line therapy in patients unable to tolerate or who have contra- indications to the first-line antibiotics (oral)	azithromycin	500 mg daily	10 mg/kg/day to a maximum of 500 mg daily	7 days for EM
First-line therapy - intravenous	ceftriaxone	2000 mg daily	50 to 75 mg/kg/day to a maximum of 2000 mg daily	14 to 21 days for neurologic manifestations 14 days for carditis 14 days for arthritis
/// Second-line therapy in patients unable to tolerate or who have contra- indications to the first-line intravenous antibiotics	/// ceftriaxone	/// 2000 mg TID	/// 150 to 200 mg/kg/day divided into three or four doses up to a Max of 6000 mg daily	/// 14 to 21 days for neurologic manifestations
	penicillin G	18 to 24 million units are divided every four hours	200,000 to 400,000 units are divided every four hours, to a maximum of 18 to 24 million units	14 to 21 days for neurologic manifestations

In early localized or early disseminated Lyme disease associated with EM, the guidelines recommend azithromycin as a second-line agent for patients who cannot tolerate or have contraindications to first-line antibiotics. Some, but not all, studies show azithromycin and first-line antibiotics have equal efficacy.¹⁹

The IDSA guidelines do not address pregnant or nursing women with early localized or early disseminated Lyme disease.¹⁹ Doxycycline is generally avoided during pregnancy because it can affect the fetus. Treatment for pregnant women is similar to that of non-pregnant adults and includes oral amoxicillin or oral cefuroxime axetil for two to three weeks.⁵⁴

For the treatment of Lyme arthritis, the guidelines recommend 28 days of oral antibiotics. If patients respond partially and have mild residual joint swelling, an additional course of oral antibiotics may be necessary; the prescriber should first exclude other causes of arthritis and determine whether the patient is adhering to the prescribed medication. If patients do not respond to the initial course of antibiotics and continue to have moderate-to-severe joint swelling, prescribers should consider two to four weeks of IV ceftriaxone.¹⁹

Some patients do not respond to any antibiotic regimen and develop post-antibiotic Lyme arthritis. Clinicians need to involve a rheumatologist if this is the case. Rheumatologists may prescribe nonsteroidal anti-inflammatory drugs, intra-articular corticosteroids, disease-modifying antirheumatic drugs, biologic response modifiers, or synovectomy (a surgical procedure to remove the inflamed synovium), depending on the patient's symptoms.¹⁹

Healthcare providers must immediately treat patients with suspected Lyme carditis with appropriate antibiotics. Waiting for test results to treat is unwise. Patients with carditis can often be managed with oral antibiotics as outpatients, but should be hospitalized if symptoms are severe.³⁸ Lyme carditis requires antibiotic treatment for 2 to 3 weeks. In the most difficult cases (e.g., first-degree atrioventricular block with PR prolongation exceeding 200 msec, other arrhythmias, or clinical manifestations of myopericarditis, such as symptoms of left ventricular dysfunction), patients require hospitalization. The inpatient team will need to monitor the patient continuously. Here, IV ceftriaxone is indicated until the team sees evidence of improvement, after which patients can be switched to oral antibiotics to complete treatment.¹⁹ If patients develop bradycardia, the guidelines recommend temporary pacing rather than surgically inserting a pacemaker because symptoms tend to improve within a few days.¹⁹

POINT TO PONDER: What are the best ways you can help patients who have questions about Lyme disease?

Implications for Pharmacy Teams

When patients suspect they have, or are diagnosed with, Lyme disease, they may have questions and visit the pharmacy for help. Pharmacists and technicians can help in a number of ways. For patients who are suspected of having Lyme disease, pharmacy teams should consider establishing a file of documents that may be helpful. Table 2 provides links to materials that can help patients prevent tick exposure, use appropriate tools and techniques for tick removal, identify a tick by species, and understand Lyme disease. Many OTC Lyme tests are now available at reasonable prices, and patients can order them online or purchase them at pharmacies. Pharmacy teams should also be familiar with or ask to see online Lyme disease testing sites and be able to discuss how testing proceeds and its limitations (as discussed above).⁵⁵

Table 2

Patient Resources for Tick Bites and Lyme Disease

Organization	Material Provided
American Lyme Disease Foundation https://aldf.com/	Provides an overview of Lyme disease in patient-friendly language. Has links to clinical trials
Centers for Disease Control and Prevention https://www.cdc.gov/lyme/index.html	Comprehensive information about Lyme disease Includes a brochure and a poster describing Erythema migrans Also includes materials targeted at children
The Lyme Disease Association https://lymediseaseassociation.org/	Includes brief synopses of newsworthy items and clinical trials Has a section on ticks with photos Includes a video on tick removal

As always, when antibiotics are needed, screening can prevent adverse outcomes. At each pharmacy visit, pharmacy technicians can ask whether anything has changed medically since the patient’s last visit. They can also confirm the patient’s allergies. Pharmacists and other clinicians should note that researchers have identified many cases of biliary disease (cholecystitis, cholelithiasis, or a cholecystectomy) within 90 days of receiving high-dose ceftriaxone for presumptive Lyme disease, especially in children.²⁹ In addition, they should note that “chronic Lyme disease” is a vague diagnosis with no treatment guidelines. Long-term or inappropriate antibiotic use for “chronic Lyme disease” has been associated with septic shock, Clostridium difficile colitis, osteodiscitis (inflammation between the intervertebral discs of the spine), abscess, and death.⁵⁶

Each antibiotic used to treat Lyme disease has a specific set of potential adverse effects. Pharmacy staff should not expect patients to read the typical long patient information handouts generated by the computer. Point out key issues (e.g., doxycycline can cause cutaneous photosensitivity that may be severe) and highlight them on the handouts.

If patients are hospitalized, the prescriber can switch patients to oral therapy when they are stabilized or discharged to complete the course.^34,35 When different durations of antibiotics are shown to be effective for the treatment of Lyme disease, the shorter duration is preferred to minimize adverse effects, including infectious diarrhea and antimicrobial resistance.⁵⁷

Encouraging and monitoring adherence is critical. Applying appropriate auxiliary labels and counseling the patient to take the medication precisely as prescribed can improve outcomes. Pharmacy teams should recommend using adherence tools, such as cell phone alarms or medication boxes, to ensure complete adherence.

Talking to patients about their symptoms can be beneficial, too. For example, eye drops or an eye patch may be needed to prevent dry eyes in patients with facial palsy who cannot close one or both eyes.³⁴ Recommending appropriate analgesics based on the patient’s age or comorbidities is also helpful. Gently asking all patients with suspected Lyme disease about cardiac symptoms—e.g., palpitations, chest pain, lightheadedness, fainting, shortness of breath, and difficulty breathing with exertion—may identify serious symptoms early.^37,38

Reminding patients that pets often carry ticks inside (and can be infected with Lyme disease) is critical. Owners need to ensure their dogs are on an effective tick preventive year-round (some owners mistakenly think they can stop the preventive in the colder months; that is a bad idea).

Knowing which insecticides are effective for ticks is also important. The CDC recommends treating clothing and gear with products containing 0.5% permethrin. The Environmental Protection Agency (EPA) produces and maintains a list of registered insect repellents effective against ticks; the list includes repellents containing DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE, which must not be used on children younger than 3), para-menthane-diol (PMD), or 2-undecanone. The EPA also provides a search tool that helps individuals find appropriate products (see https://www.epa.gov/insect-repellents/find-repellent-right-you). The patient provides the pharmacy staff with how much time they will be outside and which organism they want protection against, and the search engine does the rest.

Finally, pharmacy teams should be clear with patients that contracting Lyme disease and developing antibodies do not confer protection against further exposure to Borrelia burgdorferi. Often, patients think that they have a recurrent disease from the initial tick bite or that the antibiotics are ineffective. However, studies have found that, in most cases, the tick genotype associated with new symptoms differs, indicating a new infection.⁵⁸ Ticks also carry other pathogens that cause dangerous diseases (i.e., anaplasmosis, babesiosis, ehrlichiosis, and others). They must continue to use preventive strategies.

Summary

Scientists have unraveled many of the mysteries of tick-borne disease. Unfortunately, tick-borne disease remains a national concern. In the U.S., the white-footed mouse is the primary animal reservoir (the infectious pathogen’s long-term host) for Lyme disease, and in the northeastern U.S., chipmunks, short-tailed and masked shrews (small mouse-like rodents), and eastern gray squirrels are also reservoirs.

Prevention, early diagnosis, and adequate treatment are the keys to better outcomes. When assessing patients for Lyme disease, the CDC recommends healthcare professionals use a pre-test probability assessment that includes three questions: Has the patient been in an area where Lyme disease is common? Was the patient likely exposed to ticks? Does the patient have symptoms characteristic of Lyme disease?

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