Lyme Disease Guidelines for Minnesota Clinicians: Epidemiology, Microbiology, Diagnosis, Treatment and Prevention

September 1995, Updated June 2003

Color slides have been added to these Guidelines. Clicking on an underlined word may take you to a slide. You may return to this document by using your back button.

This document was developed by the Minnesota Department of Health's (MDH) Lyme Disease Provider Education Work Group. Members included: Allan Kind, M.D., (Chair), Eric Schned, M.D., (Co-chair), Fred Anderson, B.S., Richard Andersen, M.D., Jesse Goodman, M.D., Linda Hamilton, P.H.N., JoAnn Heltzel, Ph.D., Russell Johnson, Ph.D., Barbara Jones, R.N., Ronald Menk, M.D., David Neitzel, M.S., David Persing, M.D., Ph.D., Michael Pullen, D.V.M., Dan Sawyer, Gerald Schrock, M.D., Linda VanEtta, M.D.

For further information, please contact MDH Acute Disease Epidemiology at 651-201-5414.

Select a topic from the Table of Contents:
OVERVIEW
  Background
  Etiology
EPIDEMIOLOGY
  Lyme Disease Surveillance
  National Surveillance Case Definition
  Reporting Patients with Lyme Disease to the Minnesota Department of Health
  Epidemiology in Minnesota
  Epidemiology in the United States
DIAGNOSIS
  Clinical Manifestations
  Laboratory Diagnosis
  Serologic Diagnosis
  Laboratory Performance
  Early Localized and Early Disseminated Lyme Disease
  Late Persistent Lyme Disease
  False Negative and False Positive Serologic Test Results
  Western Blot
  Western Blot Interpretation
  Spirochete Detection
TREATMENT AND FOLLOW-UP
  Prophylaxis for Tick Bites
  Erythema Migrans and Early Febrile Symptoms
  Table 3: Erythema Migrans and Early Febrile Symptoms
  Table 4: Neurologic, Cardiac and Rheumatologic Manifestations
  Asymptomatic Seropositive Patients
  Lyme Disease During Pregnancy
  Considerations for Treatment Failures
  Table 5: Late Persistent Lyme Disease and Approaches to Differential Diagnosis
  Reevaluation of the Original Diagnosis
  Reevaluation of the Patient's Initial Treatment Regimen
  Observation for Signs of Relapse, Ongoing Infection or Reinfection
  Observation for Symptoms of Lyme Disease Sequelae
  Consideration of Coinfection
PREVENTION
  Tick Habitat
  Tick Removal
  Personal Preventive Measures
  Tick/Insect Repellents
  Vaccine (LYMErix)
OTHER TICK-BORNE DISEASES
  Ehrlichiosis
  Babesiosis
  Rocky Mountain Spotted Fever
REFERENCES


OVERVIEW

Background

Lyme disease is a tick-borne, multi-systemic inflammatory disease caused by the spirochete Borrelia burgdorferi. The most common clinical manifestation is a skin lesion, erythema migrans (EM), followed in some patients by neurologic, cardiac, or rheumatologic abnormalities.

EM (formerly known as erythema chronicum migrans, or ECM) was first described in the United States in 1970 in north central Wisconsin. In 1975, an unusually high incidence of juvenile arthritis was reported in Old Lyme, Connecticut, which prompted an evaluation by Steere et al. Arthropod bites and ECM were recognized prior to onset of arthritis. This clustering and subsequent investigations identified Ixodes scapularis (formally called Ixodes dammini) as a tick vector. In 1982, a spirochete was isolated as the causative organism and given the name Borrelia burgdorferi. Lyme disease was first reported in Minnesota in 1980 when eight residents were identified with EM. Exposure occurred in counties consistent with the geographic distribution of I. scapularis.

Return to Table of Contents

ETIOLOGY

B. burgdorferi is a slow growing pathogen with a generation time of 12-24 hours in laboratory media. The cells are slender (0.2-0.25 m x 8-30 m) and are best visualized with Giemsa stain. The organisms stain poorly, if at all, on Gram stain. They are readily killed by drying and exposure to disinfectants. B. burgdorferi has the same basic structural features and unique motility shared by other spirochetes. The internal location of flagella, in combination with the spirochetes' ability to bind and activate host-derived proteases, may facilitate their rapid dissemination in the host. The spirochete is not known to produce any toxins. The pathology associated with Lyme disease may be the result of spirochetes stimulating the production of cytokines by the host. B. burgdorferi can persist in untreated patients for months to years.

The common names for I. scapularis in Minnesota are deer tick (deer tick 2), black-legged tick and bear tick. Tick infection occurs when larval ticks feed on small rodents harboring B. burgdorferi and remain infected through their development into nymph and adult stages. Infected nymphs and female adults subsequently infect other animals and humans. Migratory birds and animals may carry ticks into new habitats.

Animal studies indicate that the deer tick needs to be attached for 24 hours or more before transmission of B. burgdorferi occurs. Currently, there is no evidence to support person-to-person transmission. Transplacental transmission has been reported but epidemiologic studies suggest that adverse birth outcomes, if they occur, are rare. Transmission of B. burgdorferi through transfusion of blood obtained from an infected donor has not been reported; however, blood-borne transmission is theoretically possible.

Return to Table of Contents

EPIDEMIOLOGY

Lyme Disease Surveillance

The Minnesota Department of Health has conducted surveillance for Lyme disease since 1982; it has been a legally reportable disease in the state since 1985. The purpose of Lyme disease surveillance is to determine areas of B. burgdorferi transmission within the state and to monitor trends in disease occurrence over time. Surveillance in Minnesota is primarily passive through physician and laboratory reporting. However, laboratories that test samples from Minnesota residents are included in an active surveillance effort.

The National Surveillance Case Definition for Lyme disease includes a person with:

  • Physician-diagnosed EM (solitary lesion must be > 5 centimeters in diameter), or
  • At least one late manifestation (neurologic, cardiac, or rheumatologic), and
  • Laboratory confirmation of infection.

For surveillance purposes, MDH accepts positive results of serologic testing conducted by the Centers for Disease Control and Prevention (CDC) or a positive Western blot from a clinical reference laboratory as confirmation of infection.

Reporting Patients with Lyme Disease
All patients (acute and chronic) with suspected or confirmed Lyme disease should be reported to the Minnesota Department of Health at the following address:

Minnesota Department of Health
Acute Disease Investigation and Control

PO Box 65475
St. Paul, MN 55164-0975
Phone: 651-201-5414 Fax: 651-201-5743

more about Reporting Lyme Disease


Epidemiology in Minnesota

A cumulative total of 4,545 cases of Lyme disease meeting the surveillance case definition have been reported to the MDH since 1995. Approximately one-half of these cases were reported in residents of the Twin Cities metropolitan area; however, most exposures likely occurred in north central and eastern parts of Minnesota or western Wisconsin (See High Risk Areas for Tick-borne Diseases in Minnesota).

Within the Twin Cities metropolitan area, exposure to deer ticks has primarily occurred in Washington, Anoka, and northern Ramsey counties. This geographic pattern resembles tick surveillance studies and is consistent over time. Onset of illness most frequently occurs from May through September. I. scapularis ticks feed from March through November (See Reported Cases of Lyme Disease by Onset of Illness).

Epidemiology in the United States

Lyme disease is the most commonly reported vector-borne illness in the United States. Cases occur primarily in three distinct regions: the Northeast (from Massachusetts to Maryland), the Midwest (Minnesota and Wisconsin), and in the West (California and Oregon).

Return to Table of Contents

DIAGNOSIS

Clinical Manifestations

The clinical spectrum of Lyme disease is commonly described as early localized, early disseminated and late persistent disease; however, individual presentations may vary.

Often the first sign of early localized disease is Erythema Migrans (EM). The rash (rash 1, rash 2) occurs 3 to 30 days following exposure (median, 7 days) and is typically described as an erythematous annular border that gradually expands with partial central clearing. Patients may also experience constitutional symptoms and regional lymphadenopathy (See Table 1). If untreated, EM will resolve within a median of 28 days (range, 1 day to 14 months); treated, EM will diminish within several days after initiating therapy.

Days or weeks following the onset of illness, the organism disseminates through the bloodstream. Multiple skin lesions may occur but appear smaller. Constitutional symptoms and generalized lymphadenopathy are common. Within several weeks to months, some patients experience signs of neurologic, cardiac, or rheumatologic involvement. Untreated or inadequately treated patients may experience late persistent Lyme disease months to years following the onset of illness. Signs uncommonly or possibly associated with Lyme disease are shown in Table 2.

Table 1. Signs and Symptoms Strongly and/or Commonly Associated with Lyme Disease

Stage of Disease Signs and Symptoms Patients with Findings (%)*
Early Localized Disease Erythema migrans (localized lesion) 60-801
Constitutional symptoms (minor)
- low grade fever

--
--
Lymphadenopathy (regional) 412
Early Disseminated Disease Erythema migrans (multiple lesions) 482
Constitutional symptoms
- malaise, fatigue, and lethargy
- headache
- fever and chills
- stiff neck
- arthralgias
- myalgias

802
642
592
482
482
432
Lymphadenopathy (generalized) 202
   Rheumatological Intermittent arthritis
(especially knees and other large joints)
51-602,3
Arthralgias 483

   Neurological Meningitis**
15-202
Cranial neuritis (facial palsy) --
Radiculoneuropathy --
Subtle encephalopathy --
   Cardiac Atrioventricular block
4-82
Late Persistent Disease Chronic arthritis
(may be associated with joint erosion)
--
Neurological impairment --
Fatigue --

* Percentages are study-specific and not population-based.
-- Specific percentages are unavailable
** The meningitis associated with Lyme disease typically has a lymphocytic pleocytosis.
1-3 See References

Table 2. Signs Uncommonly or Possibly Associated with Lyme Disease*

Stage of Disease

System

Signs

Early Localized and
Early Disseminated Disease

Neurologic

mononeuritis multiplex1, chorea1 cerebellar ataxia1
Ophthalmic conjunctivitis1 and a variety of other findings1,4
Genitourinary hematuria or proteinuria1, orchitis1
Late Persistent Disease Dermatologic
Musculoskeletal
acrodermatitis chronica atrophicans1
periostitis or joint subluxation below lesions of acrodermatitis1
Neurologic chronic encephalomyelitis1, axatic gait1, chronic axonal polyradiculopathy1
Psychologic cognitive impairments5, dementia1, verbal memory impairment5, depression6
Ophthalmic keratitis1, and a variety of other findings1,4
1-6 See References.
*Signs outlined in Table 2 are conditions that have been reported in persons diagnosed with Lyme disease; however, they are not typical of Lyme disease and it is not known if they are caused by B. burgdorferi infection.

Return to Table of Contents

LABORATORY DIAGNOSIS

Serologic Diagnosis

Serology is the most useful laboratory test that is readily available as an adjunct to the clinical diagnosis of Lyme disease. Serologic results must be used in combination with clinical history, patient presentation and an understanding of the antibody response in Lyme disease.

Laboratory Performance

Serologic testing in Lyme disease can be performed with a high degree of sensitivity and specificity. However, the results may vary between laboratories because testing has not yet been standardized. This lack of standardization has resulted in false negative and false positive results.

To minimize these testing discrepancies, CDC and the Association of State and Territorial Public Health Laboratory Directors recommend a two-step confirmation process be used for all serum specimens. Specimens should first be tested by using a sensitive screening test, such as the enzyme-linked immunosorbent assay (ELISA) or the indirect immunofluorescence assay (IFA). All samples judged to be equivocal (borderline) or positive should then be confirmed by Western blot.

Early Localized and Early Disseminated Lyme Disease

Negative ELISA or IFA results are rare but can occur when specimens are obtained before the patient has developed a significant antibody response (days to weeks).

Approximately one-half of patients who present with EM will be seronegative. The probability that a patient will be seropositive increases the longer EM is present and the more marked the clinical manifestations. Both IgM and IgG antibody response occur in early Lyme disease.

Initiation of adequate antibiotic treatment will abort the antibody response in about 20% of patients. The remainder will become seropositive after 8 to 12 days. Although most adequately treated patients will have a declining antibody titer, approximately 17% of successfully treated patients will remain seropositive by ELISA or IFA at least one year after treatment 7. Antibody titer cannot be used to monitor patient response to therapy. If seronegative patients experience symptoms following treatment, a convalescent sample may assist with confirmation of the original diagnosis.

Late Persistent Lyme Disease

Generally, untreated patients with late persistent Lyme disease, particularly those with arthritis, will develop a strong humoral immune response with a predominance of IgG antibody. Detectable IgG antibody may persist for years despite successful antibiotic treatment. Treated patients usually have slowly decreasing antibody titers. In neuroborreliosis, antibody testing of CSF can be useful because specific IgM or IgG antibody may be produced intrathecally.

False Negative and False Positive Serologic Test Results

False negative ELISA or IFA results are rare but can occur when the serologic assay lacks adequate sensitivity. False positive ELISA or IFA results can occur if a laboratory is deficient and/or if the patient has certain other infections (e.g., infectious mononucleosis or endocarditis). These infections can result in the formation of a variety of antibodies which may cross-react with B. burgdorferi antigens. Patients with syphilis will frequently have false positive tests for Lyme disease; however, these patients will have positive VDRL tests, whereas Lyme disease patients do not. Some patients with autoimmune disease may also have false positive serologic tests for Lyme disease.

Western Blot

The Western blot is used to confirm equivocal and positive serology results obtained by ELISA or IFA. It should not be used as a screening test. This assay detects the presence or absence of antibody and is not quantitative. During the first 4 weeks after disease onset, both IgM and IgG serologic tests should be performed. Persons with disseminated or late persistent disease almost always have a strong IgG antibody response. Antibody can be detected with Western blot years after successful treatment.

Western Blot Interpretation

According to CDC's Morbidity and Mortality Weekly Report (MMWR™) 1995; 44 (31):590-591, an IgM immunoblot is considered positive if two of the following three bands are present:

  • 24 kDa (OspC)
  • 39 kDa (BmpA)
  • 41 kDa (Fla)

An IgG immunoblot is considered positive if five of the following 10 bands are present:

  • 18 kDa
  • 21 kDa (OspC)
  • 28 kDa
  • 30 kDa
  • 39 kDa (BmpA)
  • 41 kDa (Fla)
  • 45 kDa
  • 58 kDa (not GroEL)
  • 66 kDa
  • 93 kDa 8

For further information on Western blot interpretation, contact an infectious disease specialist or a reference laboratory.

Spirochete Detection

In certain situations, culture of B. burgdorferi may be useful. Culture of skin biopsy material taken from a suspect EM lesion provides the highest yield (up to 86% positive)9. Cultures of blood, CSF, and synovial fluid are less successful. A selective media for culturing B. burgdorferi is available through a reference laboratory.

Polymerase chain reaction (PCR) is capable of detecting extremely small numbers of the spirochete in blood, CSF, synovial fluid, and skin biopsies. A potential problem with PCR is its extreme sensitivity leading to false positive serologic test results. PCR testing is still largely investigational and should only be performed by an experienced research facility.

Return to Table of Contents


TREATMENT AND FOLLOW-UP

Prophylaxis for Tick Bites

The risk of contracting Lyme disease from a tick bite is small, even in endemic areas where ticks may be heavily infected, especially if the tick is promptly and properly removed after attachment. Use of prophylactic antibiotics is generally not recommended, but should be considered on a case-by-case basis.

Erythema Migrans and Early Febrile Symptoms

Most patients treated for EM do remarkably well, with infrequent objective evidence of failure. Effective drugs for EM and early febrile illness include doxycycline, amoxicillin, penicillin, tetracycline, and cefuroxime axetil (See Table 3).

Neurological, Cardiac and Rheumatological Manifestations

For patients with objective neurologic abnormalities, with the possible exception of facial palsy alone, parenteral antibiotic therapy is necessary (Table 4). Corticosteroids may be beneficial with cardiac manifestations if the patient does not respond within 24 hours after initiating antimicrobial therapy. Intra-articular corticosteroids may be detrimental in infected joints and should be avoided.

Asymptomatic Seropositive Patients

No current evidence suggests that a seropositive patient who is truly asymptomatic should be treated with antibiotics.

Lyme Disease During Pregnancy

Although there is great concern about congenital Lyme disease, the risk of maternal-fetal transmission is very low. The appropriate treatment for Lyme disease during pregnancy is unclear. It may be sufficient for pregnant patients to receive the same drugs and dosage schedules appropriate for the clinical manifestations as recommended for nonpregnant patients. However, doxycycline and tetracycline should not be administered to pregnant or lactating women. Transmission of B. burgdorferi through breast milk has never been documented.

Considerations for Treatment Failures

If signs and/or symptoms persist or occur 6 months after antibiotic treatment, the patient may have late or persistent Lyme disease. At this time, the clinician should consider the following:

  1. Reevaluation of the original diagnosis
  2. Reevaluation of the patient's initial treatment regimen
  3. Observation for signs of relapse, ongoing infection or reinfection
  4. Observation for symptoms of Lyme disease sequelae (post-infectious process),
    and
  5. Consideration of Co-infection.

Reevaluation of the Original Diagnosis

A common reason for treatment failure is misdiagnosis. Based on the clinical presentation, a careful evaluation may need to be performed for a broad range of other diagnostic possibilities. Serologic testing should be repeated in a reference laboratory and equivocal or positive serologic results should be confirmed by Western blot.

Reevaluation of the Patient's Initial Treatment Regimen

The cause of persistent symptoms may be due to prior improper or inadequate therapy. In this circumstance, retreatment should be considered.

Observation for Signs of Relapse, Ongoing Infection or Reinfection

A "relapse" refers to persistent or recurrent objective signs of active infection or inflammation following appropriate antibiotic treatment. In general, except for meningitis or central nervous system (CNS) by parenchymal disease confirmed by diagnostic testing, repeated courses of parenteral therapy are not advised given the significant risks (e.g., infection, anaphylaxis, and gallstones). Oral therapy is preferred.

In confirmed seropositive patients with persistent findings unexplained by other diagnoses, additional course(s) of antibiotics may be considered. The following criteria are suggested guidelines: Consider retreatment with the same medication regimen employed initially in Table 3
or Table 4, or

  1. Treat with a full alternative recommended regimen in Table 3 or Table 4, or
  2. If an oral regimen was used for initial treatment (See Table 3), consider using a recommended parenteral regimen (See Table 4).
  3. Adjunct therapy with anti-inflammatory agents and/or antidepressant medication may also be helpful, where clinically appropriate.
  4. Persistent synovitis due to Lyme disease, which does not respond to antibiotics may improve after arthroscopic synovectomy.

A negative antibody test is rare in late persistent Lyme disease; therefore, other diagnostic possibilities need to be very aggressively pursued. In rare instances where Lyme disease is highly suspected (e.g., objective arthritis or meningitis without other cause in a patient with a history of EM who resides in an endemic area), an observed trial parenteral therapy may be advisable. Repeated courses of parental therapy are not recommended in seronegative patients given the known risks and unproven benefits.

Apparent responses to repeated courses of therapy in both seropositive and seronegative patients have many possible explanations which need consideration. These include not only treatment of late persistent Lyme disease but also placebo effect, effects on other misdiagnosed or unknown illnesses, and nonspecific drug effects (e.g., anti-inflammatory effect). In all cases, the patient needs careful periodic examination, assessment and follow-up. The development of new or progressive symptoms should not automatically be ascribed to Lyme disease.

Subsequent reinfection may occur in patients treated with antibiotics early in the course of their illness; however, reinfection has not been observed in patients with the expanded immune response associated with late Lyme disease (suggesting that protective immunity can be achieved with natural infection). 6, 15, 16 Standard treatment recommendations for the appropriate stage of Lyme disease are indicated.

Observation for Symptoms of Lyme Disease Sequelae

Some individuals with persistent or recurrent symptoms without objective findings may have a post-infection process. Other mechanisms (e.g., immunologic, metabolic, post-inflammatory, psychologic, etc.) may be involved. Antibiotics have not been effective for patients with Lyme disease sequelae. Other treatment approaches are indicated. Careful ongoing assessment for the evolution of features of "relapse" are indicated (e.g., new IgM response), although this is believed to be rare.

Consideration of Co-infection

Co-infection with pathogens of the piroplasm family (Babesia microti) and/or the rickettsia genus Ehrlichia should be considered in patients with early localized or early disseminated Lyme disease who fail to respond to treatment. Co-infection should also be considered in patients who present with severe Lyme disease or sequelae of Lyme disease, although there is currently no proof that these pathogens play a major role in chronic symptoms of previously treated patients. All three zoonoses are transmitted by the same Ixodes tick, and may perhaps be transmitted through the same tick bite.

Table 3. Erythema Migrans and Early Febrile Symptoms
Adult and Pediatric Dosages
  Drug Adult Dosage Pediatric Dosage
First Line* Doxycycline




Amoxicillin
100 mg p.o. bid x 14-30 days10(not safe in pregnancy)


500 mg p.o tid x 14-30 days11(safe in pregnancy)
(>9 yrs) 100 mg p.o. bid x 14-30 days13



(<9 yrs) 25-50 mg/kg/day p.o. divided into 3 doses x 14-21 days (max 1-2 g/day)13
Alternatives** Penicillin





Cefuroxime axetil
500 mg p.o. qid x 14-30 days12(safe in pregnancy)



500 mg p.o. bid x 14-30 days10 (safe in pregnancy)
(<9 yrs) 25-50 mg/kg/day p.o. divided into 3 doses x 14-21 days (max 1-2 g/day)13

N/A
Second Line*** Erythromycin 500 mg p.o. qid x 1418 days12 (safe in pregnancy) N/A
1013 See References * First Line -- Doxycycline and amoxicillin may have pharmacokinetic advantages over penicillin V. (Tetracycline 250-500 mg p.o. qid may also be used in patients >9 years old.10)
** Alternatives -- Doxcycline, penicillin V and amoxicillin are less expensive than cefuroxime axetil.
***Second Line -- Erythromycin is not as effective as other agents.
Doxycycline is preferred when a patient is febrile after a tick bite and no EM is present or if clinical and/or laboratory findings are suggestive of ehrlichiosis. These guidelines may be modified by new findings and should always be applied with close attention to the clinical course of the patient. Please consult a specialist for further recommendations on the diagnosis and treatment of Lyme disease, especially in special circumstances (e.g., pregnancy).

Table 4. Neurologic, Cardiac and Rheumatologic Manifestations Adult and Pediatric Dosages

  Drug* Adult Dosage Pediatric Dosage
I. Neurologic Manifestations
A. Isolated Facial Palsy
First Line Oral Regimens Same as for EM and early febrile illness14 (use for at least 21 days) Same as for EM and early febrile illness13
B. Meningitis, Encephalitis,
Radiculoneuropathy,
Peripheral neuropathy

First Line

Ceftriaxone 2 g IV q d x 14-28 days10 75100 mg/kg/day IV or IM x 14-21 days (max 2 g/day)13

Alternative

Cefotaxime 2 g IV q 8h x 14-28 days11 N/A

Second Line

Penicillin G 5 million units IV q 6h x 14-28 days11 N/A
II. Cardiac Manifestations Ceftriaxone




Penicillin G
(2 g IV q d x 14-28 days 10)



(5 million units IV q 6h x 14-28 days11)

Mild carditis: Same as for EM and early febrile illness (oral regimen)13


Severe carditis: Penicillin G 300,000 U/kg/IV in divided doses q 4h (max 20 MU/day)13

or

ceftriaxone 75100 mg/kg/day IV or IM x 14-21 days (max 2 g/day)13


III. Rheumatologic Manifestations
First Line Doxycycline or Amoxicillin Same as for EM and early febrile illness10 (use for at least 30 days); course of treatment may need to be repeated Same as for EM and early febrile illness (use for at least 30 days)13

If no response to oral antibiotics

First Line Ceftriaxone 2 g IV q d x 14-21 days14 75100 mg/kg/day IV or IM x 14-21 days (max 2 g/day)13
Alternative Penicillin G 5 million units IV q 6h x 14-21 days13 300,000 U/kg/day IV in divided doses q 4h x 14-21 days (max 20 MU/day)13
At this time, there is no scientific evidence to support long-term parenteral therapy; however, controlled trials have not been done. Please consult a specialist for further recommendations on the diagnosis and treatment of Lyme disease, especially in special circumstances (e.g., pregnancy)

*Although the optimum duration of treatment has not been established, 10-30 days of treatment has been recommended.11 The Work Group's suggested regimen is 14 days.

Table 5. Late Persistent Lyme Disease and Approaches to Differential Diagnosis

Late Persistent Lyme Disease, Seropositive Sequelae of Lyme Disease, Seropositive (Etiology Uncertain) Possible Sequelae of Lyme Disease, Seronegative (Etiology Uncertain) Possible Sequelae of Lyme Disease, Seronegative, (Etiology Uncertain) Asymptomatic Seropositive (Etiology Uncertain)
Objective signs

-rheumatologic
-neurologic
-ophthalmic
-dermatologic
Subjective symptoms

-arthralgia
-myalgia
-fibromyalgia
-fatigue
-psychologic
Subjective symptoms

-rheumatologic
-neurologic
Subjective symptoms

-arthralgia
-myalgia
-fibromyalgia
-fatigue
-psychologic
No objective signs or subjective symptoms

-asymptomatic
Questions to Ask:

Was the initial treatment regimen adequate? Is the patient reinfected? Is there an additional diagnosis?

Questions to Ask:

Was the initial diagnosis correct? Was the initial treatment regimen adequate? Is the serology a false-positive? Has a new problem developed?

Questions to Ask:

Does the patient have any history of tick exposure? Was the initial diagnosis of Lyme Disease correct?

Questions to Ask:

Was the initial diagnosis correct? Are other diagnoses being considered? Is there a co-existent infection?

Questions to Ask:

Why was the serology ordered? Is the patient truly asymptomatic?

Considerations:

A. Relapsing disease
1. Reevaluation of the initial treatment regimen;
2. Relapse, ongoing infection or reinfection;
3. Additional diagnoses;
4. Co-infection

Considerations:

A. Misdiagnosis;
B. If the initial treatment regimen was incomplete, retreat;
C. Obtain a Western blot for confirmation of equivocal and positive ELISA or IFA tests.

Considerations:

A. If Lyme disease is suspected, consider parenteral antibiotics;
B. PCR testing or synovial fluid, CSF;
C. Careful ongoing assessment.

Considerations:

A. Additional diagnoses;
B. Other laboratory tests;
C. A trial of oral antibiotics may be considered if the patient has a history of EM or other compelling evidence for exposure.

Considerations:

A. If the serology was ordered because of a clinical problem, symptom or laboratory abnormality, further investigation is warranted;
B. If the patient is truly asymptomatic, clinical observation without antibiotic treatment is appropriate.


Return to Table of Contents


PREVENTION

Ixodes scapularis or the deer tick has a teardrop-shaped body. It is dark reddish brown, and is much smaller than the wood tick (also called dog tick -- wood tick has white markings).

Tick Habitat

Deer ticks live in wooded, brushy areas that provide food and cover for deer and small mammals such as white-footed mice. Exposure to ticks may be greatest in the woods and fringe areas next to woods such as the border of a yard.

Ticks search for a host from the tips of grasses and shrubs, not from trees. Ticks do not jump or fly; they grab onto animals or persons who brush against vegetation. The ticks feed on blood by inserting their mouth parts into the skin. Ticks are slow feeders; therefore, the risk of getting Lyme disease greatly increases the longer the tick is attached.

Tick Removal

The mouthparts of the tick should be grasped close to the skin with a tweezers or tick removal tool. A gentle pressure applied for 15-30 seconds will loosen the tick mouthparts which are cemented in place and the tick can be removed intact. The body of the tick should not be squeezed. The tick should be pulled outward gently and steadily. An antiseptic should be applied to the bite to prevent bacterial infection. The patient should be instructed to watch for early signs and symptoms of Lyme disease following tick removal. Testing of the tick for B. burgdorferi is not recommended.

Home remedies such as nail polish remover, Vaseline, gasoline, the head of a hot match or other noxious stimuli are not recommended to remove a deer tick because the deer tick cements its mouthparts into the bite and is unable to back out when confronted.

Personal Preventive Measures

Checking the body, at least daily, remains the most important preventive measure to find attached ticks. Instruct patients to lightly run their fingertips through their hair, along their hairline and over their body. An attached tick often feels like a small scab. If a tick is found it should be quickly and properly removed. A brisk toweling off after showering will remove crawling ticks before they become attached.

When walking or hiking in areas of tick habitat, patients should be instructed to walk in the center of the trail to avoid picking up ticks from grass or brush. Light-colored clothing should be worn so ticks can be seen easily. Pants should be tucked into socks or boots to prevent ticks from crawling under clothing. Long pants and long-sleeved shirts that fit tightly at the ankles and wrists should be worn along with closed-toed shoes. Dogs or other pets should be checked for ticks before allowing them to enter the house.

Tick/Insect Repellents

Permethrin is a compound that effectively repels and kills ticks. It is marketed under several brand names for use on fabric and fur. Permethrin is not intended for use on human skin, where the chemical readily breaks down. It is a neurotoxin and should only be applied on clothing. Repellents containing DEET (diethyltoluamide) are available in a wide variety of brands. However, few DEET compounds repel ticks for longer than 3 hours, and DEET's tick repellent ability is less than 100% . DEET is a neurotoxin and is readily transported across the skin and absorbed into the circulation; therefore, concentrations of 30% or less are encouraged for adult use, and 10% or less for children. Caution should be applied with use in children.

Vaccine

As of February 26, 2002, LYMErix, the only human Lyme disease vaccine has been discontinued.

Return to Table of Contents

 

OTHER TICK-BORNE DISEASES

Tick-borne diseases should be considered in patients who present with a febrile illness of unknown origin and history of a tick bite or presence in an endemic area 1 month prior to onset of symptoms. Other tick-borne diseases reported in Minnesota include human anaplasmosis, babesiosis, and Rocky Mountain spotted fever. Lyme disease, human anaplasmosis, and babesiosis are transmitted by the same Ixodes tick. The following descriptions of these diseases are provided to assist with the differential diagnosis.

Human Anaplasmosis (HA)

From 1998 to 2004, 604 cases of HA were reported in Minnesota. One hundred forty-nine of those cases occurred in 2002, a record-level of reports.

HA is a bacterial disease transmitted to humans by the same I. scapularis ticks that transmit Lyme Disease. HA was first recognized during 1993 in several patients from Minnesota and western Wisconsin. The HA agent has been named Anaplasma phagocytophilum. (Note the genus change from Ehrlichia to Anaplasma)

Onset of illness occurs within 1 to 3 weeks after exposure (typically, 11-12 days). Signs and symptoms include fever, chills, headache, and myalgias. Less frequently occurring signs and symptoms include nausea, vomiting, anorexia, acute weight loss, abdominal pain, cough, diarrhea, and change in mental status. Patients will occasionally present with a rash (maculopapular or petechial). Highly suggestive laboratory findings include: leukopenia, thrombocytopenia, unexplained anemia and increased aminotransferase levels. Hyponatremia is an additional supportive laboratory finding. Reference laboratories with skilled observers may detect intracellular inclusion in granulocytes of Wright-stained blood.

Cases respond dramatically to doxycycline therapy (100 mg bid until the patient is afebrile for at least 3 days). Other tetracycline drugs are also likely to be effective. There are no data on treatment in children younger than 9 years of age and in pregnant women (groups for whom tetracycline is routinely contraindicated).

In general, even if the diagnosis of ehrlichiosis is unproven, people with unexplained fever after a tick exposure should receive empiric doxycycline therapy, particularly if they experience leukopenia and/or thrombocytopenia.

Babesiosis

Babesia microti is a protozoan of the piroplasm family. The clinical spectrum ranges from mild and self-limited to serious. Severe infections are most common in patients who have had a splenectomy or are otherwise immunosuppressed. A gradual onset of illness may include malaise, anorexia, and fatigue followed more acutely by fever, chills, myalgias, arthralgias, nausea and vomiting. Hypotension and renal failure have been reported.

Supportive laboratory findings include: thrombocytopenia, hemolysis and hepatic dysfunction. In acutely ill patients, careful examination of blood smears by experienced individuals usually reveals intraerythrocytic parasites. Approximately 20% of patients diagnosed with babesiosis have concurrent infection with B. burgdorferi. Babesiosis is treated with quinine and clindamycin; treatment should be undertaken with the assistance of an infectious disease specialist.

Rocky Mountain Spotted Fever

Rocky Mountain spotted fever is extremely rare in Minnesota but isolated cases have been reported from the southern section of the state. The illness is caused by Rickettsia rickettsii, which is transmitted by the tick species Dermacentor variabilis (wood tick). Signs and symptoms include an abrupt onset of fever, malaise, headache, myalgias, nausea and vomiting, and a rash. The typical rash first appears as macules on the wrists and ankles which then spread to the trunk, face, palms, and soles.

Supportive laboratory findings include: thrombocytopenia, increased serum hepatic aminotransferase levels, and hyponatremia. The illness is treated with tetracycline in adults and chloramphenicol in children less than 8 years of age; treatment should be undertaken with the assistance of an infectious disease specialist.

Return to Table of Contents

If you have questions about tick-borne diseases, call the Minnesota Department of Health at 651-201-5414 or toll free at 1-877-676-5414.


For information on Lyme Disease from Centers for Disease Control and Prevention, please see: The CDC Lyme Disease Home Page. Attention: Non-MDH link

REFERENCES

  1. Steere AC. Lyme disease medical progress. N Engl J Med 1989; 321(9):586-590.
  2. Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983; 99:76-82.
  3. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987; 107:725-731.
  4. Bergloff J, Gasser R, Feigl B. Ophthalmic manifestations in Lyme borreliosis. J Neuro Opthalmol 1994; 14(1):15-20.
  5. Shadick NA, Phillips, PB, Logigian EL. The long-term clinical outcomes of Lyme disease. Ann Intern Med 1994; 121(8):560-567.
  6. Kaplan RF, Meadows ME, Vincent LC, et. al. Memory impairment and depression in patients with Lyme encephalopathy: Comparison with fibromyalgia and nonpsychotically depressed patients. Neurology 1992; 42:12631267.
  7. Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for sero-diagnosis of early Lyme disease. J Clin Microbiol 1995; 33:419-22.
  8. Dressler F, Whelan JA, Reinhart BN, et al. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 1993; 167:392-400.
  9. Berger BW, Johnson RC, Kodner C, et al. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J Clin Microbiol 1992; 30(2):359-361.
  10. Treatment of Lyme Disease. Med Letter Drugs Ther 1992; 34 (881):95-97.
  11. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingston, 1995; 2143-2155.
  12. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med 1995; 98 (supp 4A):4A-205.
  13. Peter G, Lepow M, McCracken G. Lyme disease: Report of the committee on infectious diseases. Am Acad Pediatr 1991; 22:296-300.
  14. Rahn D, Malawista S. Lyme disease: Recommendations for diagnosis and treatment. Ann Intern Med 1991; 114(6):472-481.
  15. Pfister HW, Neubert U, Wilske B, et al. Reinfection with Borrelia burgdorferi. Lancet 1986;11:984-985.
  16. Salazar JC, Gerber MA, Goff CW. Long-term outcome of Lyme disease in children given early treatment. J Pediat 1993; 122(4):591-593.

Updated Monday, July 07, 2014 at 09:47AM