Little Tick Bite, Big Problem: Lyme Disease Materials

LITTLE TICK BITE, BIG PROBLEM: LYME DISEASE

JEANNETTE Y. WICK, RPh, MBA, FASCP

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

Topic Overview

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 that is usually transmitted by Borrelia burgdorferi and transmitted by ticks of the genus Ixodes. Generally associated with a tick bite lasting 36 hours or more and closely associated with erythema migrans, this infectious disease is rarely fatal but often causes symptoms including arthralgias, arthritis, central nervous system complications, and a variety of 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 Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-24-024-H01-P

Pharmacy Technician  0669-0000-24-025-H01-T

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

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: March 12, 2024 Expiration Date: March 12, 2027

Target Audience: This educational activity is for pharmacists and pharmacy technicians.
 

How to Earn Credit: From March 12, 2024, through March 12, 2027, participants must:

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

Study the section entitled “Educational Activity;” and

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

Credit for this course will be uploaded to CPE Monitor®.

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 developing this activity: Jeannette

Y. Wick, RPh, MBA, FASCP, and Pamela Sardo, PharmD, BS. Pamela Sardo and Jeannette Y. Wick have no conflicts of interest or financial relationships regarding the subject matter discussed. 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 2024: 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

Little Tick Bite, Big Problem: Lyme Disease Introduction

Lyme disease has been around for centuries, but it was an unnamed culprit until a group of mothers in Connecticut became concerned about clusters of unexplained illnesses in the 1970s. Today, infectious disease specialists know considerably more about Lyme disease than they did in 1975. The bacteria spirochete Borrelia causes this vector-borne, zoonotic infection, and two species cause the disease. Borrelia burgdorferi has traditionally been the primary species of concern. While it is still the most important vector, 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 United States (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 This continuing education activity will discuss some of the disease’s history and highlight prevention, prophylaxis, and treatment options.

POINT TO PONDER:

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

History of Lyme Disease

Lyme disease is not new, although its name is relatively new. A 2010 autopsy of a Neolithic mummy discovered 5,300 years after the man died on an icy mountain found the genetic footprint of Borrelia burgdorferi in his DNA; pathologists indicated he was the earliest known human infected by the

bacteria that causes Lyme disease.3 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 bacteria from the skin from EM lesions and linked it to 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 1975.4-7 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. In children, the “new” disease rate was 100 times that of JRA. Clinical and demographic investigation suggested 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.4,6

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 1991.8 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.9

Once local and state health departments receive word of possible Lyme disease cases, they investigate them to classify the cases according to the national surveillance “case definition.”10 Confirmed or probable cases of Lyme disease are reported to the CDC through the National Notifiable Disease Surveillance System (NNDSS). The CDC has revised the “case definition” of

Lyme disease several times, most recently in 2022.10 As described above, 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.10

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. Compiling the results of 90 studies that enrolled more than 158,000 people, rates of seropositivity indicated that 20.7% of residents in Central Europe, 15.9% of residents in Eastern Asia, and 13.5% of residents in Western Europe appeared to have had Lyme disease. The rate in North America was 9%.11

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 cannot directly transmit it to humans.12

Ticks are Lyme disease’s only living agent that carries and transmits this infectious pathogen to another living organism; 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.13,14 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.15 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.15

Identifying ticks correctly 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 (which are 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 save the tick and submit it to the health department for identification.16 The SIDEBAR 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 reduce the chances of Lyme disease considerably.15

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 Correctly15,16

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.17 Insurance estimates indicate approximately 476,000 people are diagnosed or treated for Lyme disease annually in the U.S., a number that is more than 50% higher than previous estimates. The large increase is probably because so many people are treated presumptively.18 Yet the CDC records roughly 30,000 confirmed and probable cases of Lyme disease annually.17 The discrepancy between the expert estimates and the CDC’s numbers speaks to the issue of underreporting.19

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 2019.20 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.2,21

Several factors have contributed to Lyme disease’s increase in incidence and prevalence:22

Climate change has expanded the number of tick-habitable environments.

Human encroachment into habitats favorable to ticks and their hosts increases the likelihood of human exposure.

Deforestation has created a more tick-friendly environment.

Increased human outdoor activities also increase the likelihood of exposure.

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 tickborne disease are listed below.23 From the factors listed, pet ownership confers the highest risk.23

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 (jogging, walking, off-road cycling, horseback riding)

pet ownership

The issue of deer is interesting. Although settlers in the U.S., over- hunted white-tail 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 traditionally were deer-free.24,25 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 number 700 deer by 1994.24,25

POINT TO PONDER:

What risk factors for tickborne 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

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 consisting of a red ring around a clear area with a red center.23 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.26 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.27 It lasts for three to five weeks.26 Noting 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.28 Misdiagnosis or delayed diagnosis is common for this reason.29

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 cases in which 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 are able to cause Lyme disease. Another manifestation differs in European patients.30

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.31

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 to the nervous system, creating 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 ticks tend to bite children on the upper trunk and the head more often, potentially making the CNS more accessible to the spirochete.32 Other symptoms include facial palsy (facial paralysis similar to Bell’s palsy), tingling or numbness in extremities, enlarged lymph glands, abnormal pulse, sore throat, vision changes, fever (100o to 102oF), and severe fatigue.26 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.33,34 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 manifests as arthritis primarily in the large joints, especially the knee. Patients with the alloantigen HLA-DR4 have a high risk of developing chronic arthritis.35 Pharmacy staff should note that arthritis differs from arthralgia, which is simple aches or pain. Warmth, swelling from effusion, and limited range of motion are additional characteristics of arthritis.35

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:36

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 the answer to all questions is yes, the pretest probability is high, and the prescriber should initiate treatment. Healthcare providers need to use their discretion if the answer to any one of the questions is no and order serologic testing if it seems warranted.36

The CDC recommends a two-step process using the same blood sample that detects the presence of antibodies against B. burgdorferi in a patient’s blood. The first step is an enzyme immunoassay (EIA) or immunofluorescence assay (IFA)–total Lyme titer or immunoglobulin A and immunoglobulin M titers.36 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.36

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 who have mononucleosis, autoimmune states, or Treponema pallidum infection may experience false positive results; healthcare providers need to consider each patient’s medical history as they decide 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.

Pharmacy teams also need to 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 EIA concurrently or sequentially rather than in the two-step process described

above.37 Clinical tests showed that this alternative approach is as accurate as the two-tiered process.37,38

In Lyme disease’s late phases, healthcare providers can consider using joint aspiration, cerebrospinal fluid analysis, and electrocardiogram (ECG) to determine the extent of the disease.16 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.16

Most patients with Lyme disease fully recover with prompt diagnosis and treatment. Untreated Lyme disease can lead to serious health concerns, including arthritis, carditis, neurologic, and ocular manifestations.39

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 2002.40 The vaccine’s effects were short-lived, so protection has probably waned for patients vaccinated before the vaccine was discontinued. Clinicians should manage them as they do patients who never received the vaccine.17 Interest in developing a replacement vaccine appears to be growing in light of the increase in Lyme disease cases.41,42

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 round.17 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.17,13,14

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%20wh ere%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.16

POINT TO PONDER:

How would you differentiate a patient who may need prophylaxis from a patient 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%.43,44 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.45-47

The guidelines recommend a single dose of 200 mg doxycycline for adults and 4.4 mg/kg, up to a maximum of 200 mg, for children for prophylaxis.16 One change that deserves special note is doxycycline use in children.48 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 growing consensus supports its use in children.48 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 Disease16

In early localized or early disseminated Lyme disease associated with EM, the guidelines recommend azithromycin as a second-line drug in patients who are unable to tolerate or have contraindications to the first-line antibiotics. Some, but not all, studies show azithromycin and first-line antibiotics have equal efficacy.16

The IDSA guidelines do not address pregnant or nursing women with early localized or early disseminated Lyme disease.16 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.49

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 if the patient was adherent 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.16

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 upon their symptoms.16

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 in an outpatient status but should be hospitalized if symptoms are severe.34 Lyme carditis requires treatment with antibiotics for two to three weeks. In the most difficult of cases (e.g., first-degree atrioventricular block indicated by PR prolongation exceeding 200 msec, other arrhythmias, or clinical manifestations of myopericarditis such as symptoms of left ventricular dysfunction), patients need hospitalization. The inpatient team will need to monitor 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.16 If patients develop bradycardia, the guidelines recommend temporary pacing rather than surgically inserting a pacemaker because symptoms tend to improve within a few days.16

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 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 suspect 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 may be able to order them online or purchase them in 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).50

Table 2

Patient Resources for Tick Bites and Lyme Disease

As always, when antibiotics are needed, screening can prevent adverse outcomes. At every visit, pharmacy technicians can ask if anything has changed medically since the patient’s last visit. They can also confirm the patient’s allergies. Pharmacists 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.26 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.51

Each of the antibiotics employed for Lyme disease has a specific set of possible adverse effects. Pharmacy staff should not expect that patients will read the typical long patient information handouts that the computer

generates. 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.31 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.52

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 suggest using adherence tools like cell phone alarms or medication boxes to ensure complete adherence.

Talking to patients about their symptoms can be beneficial, too. For example, in patients with facial palsy who cannot close one or both eyes, eye drops, or an eye patch may be needed to prevent dry eyes.31 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.34

Reminding patients that pets often carry ticks inside (and can be infected with Lyme disease) is critical. Owners need to be certain that 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 the organism against which they want protection, and the search engine does the rest.

Finally, pharmacy teams should be clear with patients about the fact that contracting Lyme disease and developing antibodies does not provide protection against further exposure to Borrelia burgdorferi. Often, patients think that they have 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 is different, indicating a new infection.53 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 tickborne disease. Unfortunately, tickborne disease continues to be 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 providers 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?

Course 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

Insurance estimates indicate that approximately 476,000 people are diagnosed or treated for Lyme disease annually. The CDC records roughly 30,000 confirmed and probable cases annually. What accounts for the discrepancy?

Poor study design

Under-reporting

Research bias

CDC bias

A patient shows you a rash that has a clear area in its center and a ring radiating around what looks like a bite. What might this be?

Acrodermatitis chronica atrophicans

Borrelial lymphocytoma

erythema migrans

neuroborreliosis

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

Which of the following symptoms is most likely to occur in late- stage Lyme disease?

Arthritis

Bruising

Erythema migrans

Flu-like symptoms

Which of the following patients would be the ideal candidate for prophylactic antibiotics to prevent Lyme disease?

A child whose mother removed an unengaged tick from his groin; his mother is sure she removed it within 6 hours of the tick bite

A man reports hunting in the woods for 12 hours and coming home with many ticks on his clothing but no bites

A gardener who reports being bitten several times by ticks identified by the health department as garden variety dog ticks

A patient who removes an engorged Ixodes tick has been attached for at least 36 hours and lives in a highly endemic area

Which of the following would be the treatment of choice for a patient with no allergies diagnosed with Lyme disease who is having few symptoms?

Amoxicillin

Cefuroxime

Doxycycline

Phenoxy methyl penicillin

A patient is diagnosed with Lyme disease and has neurologic manifestations. The physician decides to use doxycycline. How many days should this patient be treated?

7 to 10

10 to 14

14 to 21

21 to 28

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

You really need to use tick preventive 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.

A patient comes to the pharmacy and indicates that she has ordered a Lyme disease kit online because she doesn't want to see her primary care prescriber and has to pay for the office visit. Which of the following is the most important counseling point?

Online and over-the-counter Lyme disease testing kits are more expensive than going to the doctor.

It would be good to have the pharmacist review this testing site with you so that we would know the limitations of the results.

Please be careful; there are no online testing resources for Lyme disease.

Please make sure this is an immunofluorescence assay rather than an enzyme immunoassay.

References

Josselyn A. Mayo Researchers Identify New Borrelia Species that Causes Lyme Disease. Mayo Clinic. February 8, 2016. https://newsnetwork.mayoclinic.org/discussion/mayo-researchers- identify-new-borrelia-species-that-causes-lyme-disease/. Accessed March 11, 2024.

Bratton RL, Whiteside JW, Hovan MJ, et al. Diagnosis and treatment of Lyme disease. Mayo Clin Proc. 2008;83(5):566-571.

Hall SS. Iceman Autopsy. National Geographic. November 2011. https://web.archive.org/web/20111019172457/http://ngm.nationalgeo graphic.com/2011/11/iceman-autopsy/hall-text. Accessed March 11, 2024.

Steere AC, Snydman D, Murray P, et al. Historical perspective of Lyme disease. Zentralbl Bakteriol Mikrobiol Hyg A. 1986;263(1-2):3-6. doi:10.1016/s0176-6724(86)80093-1

Stürchler D. Of Old Lyme, ticks, and new Borrelia. Travel Med Infect Dis. 2018;26:74. doi:10.1016/j.tmaid.2018.11.004

Walter KS, Carpi G, Caccone A, Diuk-Wasser MA. Genomic insights into the ancient spread of Lyme disease across North America. Nat Ecol Evol. 2017;1(10):1569-1576. doi:10.1038/s41559-017-0282-8

Elbaum-Garfinkle S. Close to home: a history of Yale and Lyme disease.

Yale J Biol Med. 2011;84(2):103-108.

Schwartz AM, Hinckley AF, Mead PS, et al. Surveillance for Lyme Disease—United States, 2008-2015. MMWR Surveill

Summ. 2017;66(22):1-12.

Centers for Disease Control and Prevention. Notifiable Disease. National Center for Health Statistics. CDC. June 26, 2023. https://www.cdc.gov/nchs/hus/sources-definitions/notifiable- disease.htm. Accessed Accessed March 11, 2024.

Centers for Disease Control and Prevention. Lyme Disease (Borrelia burgdorferi) 2022 Case Definition. CDC. August 31, 2021. https://ndc.services.cdc.gov/case-definitions/lyme-disease-2022/. Accessed March 11, 2024.

Dong Y, Zhou G, Cao W, et al. Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis. BMJ Glob Health. 2022;7(6):e007744. doi:10.1136/bmjgh-2021-007744

Salkeld DJ, Leonhard S, Girard YA, et al. Identifying the reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in California: the role of the western gray squirrel (Sciurus griseus). Am J Trop Med Hyg. 2008;79(4):535-540.

Murray TS, Shapiro ED. Lyme disease. Clin Lab Med. 2010;30:311328.

Wright WF, Riedel DJ, Talwani R, Gilliam BL. Diagnosis and management of Lyme disease. Am Fam Physician. 2012;85:1086-1093.

Centers for Disease Control and Prevention. Lyme Disease. Transmission. CDC. January 20, 2023. https://www.cdc.gov/lyme/transmission/index.html. Accessed March 11, 2024.

Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clin Infect Dis. 2021;72(1):1-8. doi:10.1093/cid/ciab049

Centers for Disease Control and Prevention. Lyme Disease. Data and Surveillance. CDC. August 29, 2022. https://www.cdc.gov/lyme/datasurveillance/index.html?CDC_AA_refVal

=https%3A%2F%2Fwww.cdc.gov%2Flyme%2Fstats%2Findex.html. Accessed March 11, 2024.

Schwartz AM, Kugeler KJ, Nelson CA, Marx GE, Hinckley AF. Use of Commercial Claims Data for Evaluating Trends in Lyme Disease Diagnoses, United States, 2010-2018. Emerg Infect Dis. 2021;27(2):499-507. doi:10.3201/eid2702.202728

Centers for Disease Control and Prevention. Lyme Disease. How many people get Lyme disease? CDC. February 9, 2024. https://www.cdc.gov/lyme/stats/humancases.html. Accessed March 11, 2024.

Lyme Disease Association. Delayed CDC Lyme Final Lyme Case Numbers for 2019 Finally Released. Lyme Disease Association, Inc. June 9, 2021. https://lymediseaseassociation.org/resources/cases-stats- maps-a-graphs/delayed-cdc-lyme-final-lyme-case-numbers-for-2019- finally-released/. Accessed March 11, 2024.

Chrobak U. Why Lyme and other tick-borne diseases are on the rise. Knowable Magazine. February 3, 2022. https://knowablemagazine.org/content/article/health- disease/2022/lyme-other-tickborne-diseases-rise. Accessed March 11, 2024.

Habegger S. Lyme disease in Canada: an update on the epidemiology. Natl Collab Cent Infect Dis Purple Pap. 2014;43.

Fischhoff IR, Keesing F, Ostfeld RS. Risk factors for bites and diseases associated with black-legged ticks: a meta-analysis. Am J Epidemiol. 2019;188(9):1742-1750.

Rawinski TJ. Impacts of White-Tailed Deer Overabundance in Forest Ecosystems: An Overview. Northeastern Area State and Private Forestry Forest Service. USDA. June 2008. https://mountainlion.org/wp- content/uploads/2021/07/PA-A-FS-Rawinski-Impacts-of-White-Tailed-

Deer-Overabundance-in-Forest-Ecosystems.pdf. Accessed March 11, 2024.

Candler EM, Chakrabarti S, Severud WJ, Bump JK. Eat or be eaten: Implications of potential exploitative competition between wolves and humans across predator-savvy and predator-naive deer populations. Ecol Evol. 2023;13(11):e10694. Published 2023 Nov 27. doi:10.1002/ece3.10694

Ettestad PJ, Campbell GL, Welbel SF, et al. Biliary complications in the treatment of unsubstantiated Lyme disease. J Infect Dis. 1995;171(2):356-361. doi:10.1093/infdis/171.2.356

NICE guideline [NG95]. National Institute for Health and Care Excellence. Lyme disease. www.nice.org.uk/guidance/ng95. Accessed March 11, 2024.

Steere AC. Lyme disease. N Engl J Med. 1989;321(9):586-598.

Aucott J, Morrison C, Munoz B, et al. Diagnostic challenges of early Lyme disease: lessons from a community case series. BMC Infect Dis 2009;9:79.

Girschick HJ, Morbach H, Tappe D. Treatment of Lyme borreliosis. Arthritis Res Ther. 2009;11(6):258.

Centers for Disease Control and Prevention. Neurologic Lyme Disease.

CDC. August 11, 2021.

https://www.cdc.gov/lyme/treatment/NeurologicLyme.html. Accessed March 11, 2024.

Girschick HJ, Huppertz HI. Treatment of Lyme borreliosis. Arthritis Res Ther. 2009;11:1-10.

Manzoor K, Aftab W, Choksi S, Khan IA. Lyme carditis: sequential electrocardiographic changes in response to antibiotic therapy. Int J Cardiol. 2009;137:167–171.

Centers for Disease Control and Prevention. Lyme Carditis. CDC. February 24, 2022. https://www.cdc.gov/lyme/treatment/lymecarditis.html. Accessed March 11, 2024.

Stanek G, Wormser GP, Gray J, Strol F. Lyme borreliosis. Lancet.

2012;379(9814):461-473.

Centers for Disease Control and Prevention. Pretest Probability of Lyme Disease. CDC. Undated. https://www.cdc.gov/lyme/resources/pdfs/lyme-1532_poster_prior- pretest-probability-testing_digital-508.pdf. Accessed March 11, 2024.

U.S. Food and Drug Administration. FDA clears new indications for existing Lyme disease tests that may help streamline diagnoses. FDA. July 29, 2019. https://www.fda.gov/news-events/press- announcements/fda-clears-new-indications-existing-lyme-disease-tests- may-help-streamline-diagnoses. Accessed March 11, 2024.

Lee-Lewandrowski E, Turbett S, Branda JA, Lewandrowski K. Evaluation of the rapid Quidel Sofia Lyme fluorescent immunoassay as a first-tier test in a modified 2-tier testing algorithm for Lyme disease: A comparison with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM assay followed by the Zeus monovalent IgM/IgG confirmatory assay. Am J Clin Pathol. 2023;160(6):599-602. doi:10.1093/ajcp/aqad094

Patton SK, Phillips B. CE: Lyme disease: diagnosis, treatment, and prevention. Am J Nurs. 2018;118(4):38-45.

Gomes-Solecki M, Arnaboldi PM, Backenson PB, et al. Protective Immunity and New Vaccines for Lyme Disease. Clin Infect Dis. 2020;70(8):1768-1773. doi:10.1093/cid/ciz872

Chomel B. Lyme disease. Rev Sci Tech. 2015;34(2):569-576.

Šmit R, Postma MJ. Lyme borreliosis: reviewing potential vaccines, clinical aspects and health economics. Expert Rev

Vaccines. 2015;14(12):1549-1561.

Elliott DJ, Eppes SC, Klein JD. Teratogen update: Lyme disease. Teratology. 2001;64(5):276-281.

Nadelman RB, Nowakowski J, Fish D, et al; Tick bite study group. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345(2):79-84.

Sood SK, Salzman MB, Johnson BJ, et al. Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis. 1997;175(4):996-999.

Piesman J, Mather TN, Sinsky RJ, Spielman A. Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol. 1987;25(3):557-558.

Piesman J, Maupin GO, Campos EG, et al. Duration of adult female Ixodes dammini attachment and transmission of Borrelia

burgdorferi, with description of a needle aspiration isolation method. J Infect Dis. 1991;163(4):895-897.

Stultz JS, Eiland LS. Doxycycline and Tooth Discoloration in Children: Changing of Recommendations Based on Evidence of Safety. Ann Pharmacother. 2019;53(11):1162-1166. doi:10.1177/1060028019863796

Centers for Disease Control and Prevention. Pregnancy and Lyme disease. CDC. January 27, 2020. https://www.cdc.gov/lyme/resources/toolkit/factsheets/Pregnancy-and- Lyme-Disease-508.pdf. Accessed March 11, 2024.

Healthline. The 3 Best At-Home Lyme Disease Tests. Healthline.

December 20, 2023. https://www.healthline.com/health/lyme-disease-

test. Accessed March 11, 2024.

Marzec NS, Nelson C, Waldron PR, et al. Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic

Lyme Disease - United States. MMWR Morb Mortal Wkly Rep. 2017;66(23):607-609. Published 2017 Jun 16.

doi:10.15585/mmwr.mm6623a3

Centers for Disease Control and Prevention. Erythema Migrans Rash.

CDC. March 1, 2022. https://www.cdc.gov/lyme/treatment/erythema-

migrans-rash.html. Accessed March 11, 2024.

Shapiro ED. Repeat or persistent Lyme disease: persistence, recrudescence or reinfection with Borrelia Burgdorferi?. F1000Prime Rep. 2015;7:11. doi:10.12703/P7-11

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