Transcript Lyme Disease

LYME
DISEASE
CASSANDRA WHITE, PHARMD, BCACP, CGP
ASSISTANT PROFESSOR OF PHARMACY PRACTICE
HUSSON UNIVERSITY SCHOOL OF PHARMACY
MAINE PHARMACY ASSOCIATION FALL CONVENTION
SEPTEMBER 12, 2015
OVERVIEW
• Epidemiology
• Disease Summary
• Stages of Lyme Disease
• Medications
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• Prevention
OBJECTIVES
• Recognize patients at risk for Lyme disease
• Explain how the infection is transmitted and diagnosed
• Differentiate the three phases of Lyme disease
• Use IDSA treatment guidelines to determine appropriate
pharmacotherapy
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• Relate key counseling points to Lyme disease patients
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EPIDEMIOLOGY
EPIDEMIOLOGY
• Most common tick-borne
illness in the United States
• 7th most common Nationally
Notifiable disease
• ~ 30,000 cases reported
annually
• Actual incidence may be
10x higher
Epidemiology of Lyme disease. UpToDate. August 17, 2015
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• 95% of cases come from
14 states
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Centers for Disease Control and Prevention, October 5, 2014. Available from: http://www.cdc.gov/lyme/stats/maps/map2013.html
MAINE
EPIDEMIOLOGY
• 1,399 confirmed & probable cases in 2014
• 105.3 cases per 100,000 people
• Almost one-half of cases in York & Cumberland counties
• # of confirmed cases in Penobscot county quadrupled from
2007 to 2011
• Highest # of cases in young children (5-14 yo) and older
adults (65+ yo)
Lyme Disease Surveillance Report – Maine, 2014. Infectious disease epidemiology report. Maine Centers for Disease Control and Prevention.
August 18, 2015. Available from: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/publications/2014-Lyme-Surveillance-Report.pdf
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• Median age = 49 yo
Maine Centers for Disease Control and Prevention, August 18, 2015
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LYME DISEASE IN MAINE
Lyme Disease Surveillance Report – Maine, 2014. Infectious disease epidemiology report. Maine Centers for Disease Control and Prevention.
August 18, 2015. Available from: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/publications/2014-Lyme-Surveillance-Report.pdf
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LYME DISEASE INCIDENCE
Lyme Disease Surveillance Report – Maine, 2014. Infectious disease epidemiology report. Maine Centers for Disease Control and Prevention.
August 18, 2015. Available from: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/publications/2014-Lyme-Surveillance-Report.pdf
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LYME DISEASE BY AGE
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DISEASE SUMMARY
LYME DISEASE
• Named for Lyme, Connecticut where it was identified in 1975
• Spirochetal infection caused by Borrelia species
• Borrelia burgdorferi in the United States
• Transmitted by bite of infected Ioxdes
scapularis ticks (black-legged “deer” ticks)
• Can involve the skin, joints, nervous system,
Lyme borreliosis. Lancet. 2012; 379:461
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and heart
American Lyme Disease Foundation, January 5, 2010
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https://www.youtube.com/watch?v=D7skqdqWYTI
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http://www.tickencounter.org/prevention/lyme_disease
DIAGNOSIS
• Diagnosis based on:
• Signs and symptoms
• A history of possible exposure to infected blacklegged ticks
• Difficult to diagnose because:
• Patient may be unaware of tick bite
• Patient may not present with erythema migrans rash
• Initial symptoms are vague and can be attributed to a
variety of different causes
• Serologic testing can be misleading
Negative in up to 60% of patients with early infection
Western Blot must be used for confirmation
Centers for Disease Control and Prevention, October 5, 2014
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STAGES OF LYME DISEASE
STAGES OF LYME DISEASE
• Early Localized
• 3-30 days
• Early Disseminated
• 3-12 weeks
• Late Disease or Chronic Disseminated
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• > 2 months
EARLY LOCALIZED
• Incubation 3 – 32 days
• Erythema migrans – bull’s eye rash in ~80% of patients
• Flu-like symptoms
• Fever, headache, fatigue, muscle aches
• Swollen lymph nodes
• Approximately 50% of untreated cases will go on to
disseminated disease
Clinical manifestations of Lyme disease in adults. UpToDate. February 5, 2013
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• Usually responds well to appropriate PO antibiotic treatment
ERYTHEMA MIGRANS (EM)
• Bull’s-eye rash at site of tick bite
• Often do not have central clearing
• Can occur days to weeks (typically
7-10 days) after a tick bite
• Sufficiently distinctive to allow
clinical diagnosis in absence of
laboratory confirmation
• Should be ≥ 5 cm
The clinical assessment, treatment, and prevention of Lyme disease. IDSA Guidelines. October 2, 2006.
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• Treatment is indicated
EARLY DISSEMINATED
• Organism spreads throughout the body by invasion
• Distinct preference for skin, heart, CNS, joints, & eyes
• Weeks to months after infection
• Organism can persist in skin for a very long time
• Characterized by multiple, often smaller EM lesions
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Sign of spirochetemia
Clinical manifestations of Lyme disease in adults. UpToDate. February 5, 2013
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• May require IV antibiotic treatment
LATE DISEASE OR
CHRONIC DISSEMINATED
• Infection stimulates an immune response that leads to
symptoms in various organs
• Arthritis
• Chronic CNS
Facial palsy
Meningitis
Difficulty thinking
Short term memory
loss
• Speech problems
• Double / blurry vision
• Tinnitus
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Seizures
Mood swings
Irritability
Depression
Disturbed sleep
Personality changes
OCD
Anxiety
Evidence-based guidelines for the treatment of Lyme disease. ILADS. 2004
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Lyme Disease Surveillance Report – Maine, 2014. Infectious disease epidemiology report. Maine Centers for Disease Control and Prevention.
August 18, 2015. Available from: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/publications/2014-Lyme-Surveillance-Report.pdf
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SYMPTOMS OF LYME DISEASE
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MEDICATIONS
PROPHYLAXIS
• A single 200-mg dose of doxycycline given within 72 hours
after a tick bite can prevent the development of Lyme disease
• CLINICAL PEARL: Tick must be attached for at least 36 hours
to cause Lyme disease
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• The time elapsed since attachment may be estimated by the
extent of the tick’s engorgement
Department of Epidemiology and Public Health, Yale School of Medicine, 2004
PROPHYLAXIS
Prophylaxis recommended if there is a confirmed tick bite and all four
criteria are met:
1.
Tick identified as an adult or nymphal I. scapularis, estimated to have
been attached for ≥ 36 hours
2.
Started within 72 hours of tick removal
3.
Local rate of infection of ticks with B. burgdorferi is ≥ 20%
4.
Doxycycline must not be contraindicated
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Doxycycline 200 mg PO x 1 dose
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Dispense TWO 100 mg capsules / tablets
Risk of disease transmission from a recognized bite is low (1-3%),
even in highly endemic areas
Risk of transmission from an unrecognized bite may be greater
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Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite, NEJM, 2001
EARLY LOCALIZED,
EARLY DISSEMINATED
Erythema Migrans (no neurologic or cardiac manifestations):
• Doxycycline 100 mg po BID x 14 days
• Amoxicillin 500 mg po TID x 14 days
• Cefuroxime axetil 500 mg po BID x 14 days
NOTE: All of the above are first-line agents. Choice of antibiotic should be tailored to the individual and take into account
the severity of the disease as well as the patient’s age, ability to tolerate side effects, clinical features, allergy profile,
comorbidities, prior exposure, epidemiologic setting, and cost.
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• Rates of cure (defined as complete resolution of s/sx’s shortly
after completion of treatment) is ~90%
EARLY LOCALIZED,
EARLY DISSEMINATED
Lyme Meningitis or Radiculopathy:
• Ceftriaxone 2 g IV daily x 14 days
Lyme Carditis:
• PO antibiotics as for erythema migrans x 14 days
The clinical assessment, treatment, and prevention of Lyme disease. IDSA Guidelines. October 2, 2006.
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• Ceftriaxone 2 g IV daily x 14 days for hospitalized patients
LATE DISEASE OR
CHRONIC DISSEMINATED
• Treatment at this stage is controversial
• Ranges from months to years
• Can result in treatment failure or adverse drug reactions
• Many patients resort to alternative therapies
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• Homeopathy, detoxification, nutritional therapies, etc.
LATE DISEASE OR
CHRONIC DISSEMINATED
Lyme Arthritis
• Doxycycline 100 mg po BID x 28 days
• Amoxicillin 500 mg po TID x 28 days
• Cefuroxime axetil 500 mg po BID x 28 days
• Ceftriaxone 2 g IV daily x 14-28 days
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Late Neurologic
DOXYCYCLINE
• Contraindications (relative):
• Pregnancy or lactation
• Children < 8 years of age
• Side Effects:
• Nausea/Vomiting/Diarrhea
• Nasopharyngitis
• Counseling Points:
• Administer with food to decrease GI upset
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Teach patient importance of adequate hydration
Report severe diarrhea (could be C. difficile)
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• Causes sun-sensitivity  use sunscreen
• May interact with oral contraceptives  use additional form of
birth control
Micromedex 2.0, Truven Health Analytics Inc. 2013
AMOXICILLIN
• Contraindication:
• Hypersensitivity (to amoxicillin or other beta-lactam)
• Side Effects:
• Nausea/Vomiting/Diarrhea (frequent)
• Rash
• Counseling Points:
• Administer with food to decrease GI upset
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Report severe diarrhea (could be C. difficile)
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• May interact with oral contraceptives  use additional
form of birth control
• Take entire prescription (remember TID dosing!)
Micromedex 2.0, Truven Health Analytics Inc. 2013
CEFUROXIME AXETIL
• Contraindication:
• Hypersensitivity (up to 10% cross-sensitivity with PCN)
• Side Effects:
• Nausea/Vomiting/Diarrhea (frequent, duration-dependent)
• Vaginitis
• Counseling Points:
• Administer with food to increase absorption
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Bioavailability: Fasting: 37%; Following food: 52%
Report severe diarrhea (could be C. difficile)
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• May interact with oral contraceptives  use additional
form of birth control
Micromedex 2.0, Truven Health Analytics Inc. 2013
CEFTRIAXONE IV
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Contraindication:
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Do not reconstitute or coadminister with
calcium-containing solutions (C/I in neonates
aged 28 days or less)
Side Effects:
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• Nausea/Vomiting/Diarrhea
• Induration, warmth, or tightness at injection site
• Thrombocytosis
Counseling Points:
Must be administered by qualified healthcare provider
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Home visits or daily hospital appointments
Not necessarily covered by insurance companies
Local and systemic risks associated with IV therapy
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Phlebitis, infiltration, infection, etc.
Micromedex 2.0, Truven Health Analytics Inc. 2013
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PREVENTION
LYME VACCINE
• A Lyme disease vaccine was discontinued in 2002 and is
no longer available
• “insufficient consumer demand” = poor sales
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• New vaccines under development
PREVENTING TICK BITES
• Be extra vigilant in the warmer months (April – September)
when ticks are most active
• Avoid direct contact with ticks when possible
• Avoid wooded and bushy areas with high grass & leaf litter
• Walk in the center of trails
• Wear protective clothing (e.g. long pants, shirts, socks)
• Repel ticks with DEET, Permethrin, or Picaridin
• 20 – 30% DEET repellants on exposed skin & clothing
• Permethrin products on clothing only
• Find and remove ticks from your body
Diagnosis, treatment, and prevention of Lyme disease in children, Pediatric Drugs, 2003 5(6) 363-372
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• Conduct a body check & shower after coming indoors
• Tumble dry clothes for an hour to kill remaining ticks
REMOVING A TICK
1. Use fine-tipped tweezers to grasp the tick as close to skin
surface as possible
2. Pull upward with steady, even pressure
• Do not twist or jerk the tick (mouth parts can break off & remain
in skin)
3. After removal, clean bite area & hands with soap & water
Tick Identifier: http://www.tickencounter.org/tick_identification
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Centers for Disease Control and Prevention, September 16, 2013
“DEER TICK” VS. “DOG TICK”
Top row: Ixodes scapularis
Left to right:
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nymph (immature)
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adult male
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adult female
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engorged adult female
Bottom row: Dermacentor
variabilis (American dog tick)
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adult male
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adult female
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engorged adult female
Lyme Disease Research Laboratory, Maine Medical
Center Research Institute, Portland, ME 04102
Adult dog ticks are not thought to transmit Lyme disease.
They are somewhat larger than adult deer ticks and have
characteristic white markings on the dorsal (top) side
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Left to right:
TICK SPECIES OF MAINE
American Dog Tick (Dermacentor variabilis)
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Bird Tick (Ixodes brunneus)
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Brown Dog Tick or Kennel Tick (Rhipicephalus sanguineus)
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Deer Tick or Black-legged Tick (Ixodes scapularis)
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Ixodes angustus
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Ixodes dentatus
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Ixodes gregsoni
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Lone Star Tick (Amblyomma americanum)
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Mouse Tick (Ixodes muris)
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Rabbit Tick (Haemaphysalis leporispalustris)
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Seabird Tick (Ixodes uriae)
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Squirrel Tick (Ixodes marxi)
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Winter Tick or Moose Tick (Dermacentor albipictus)
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Woodchuck Tick (Ixodes cookei)
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1.
UMaine Cooperative Extension: Insect Pests, Ticks and Plant Diseases. Available from: http://extension.umaine.edu/ipm/tickid/ Accessed August 17, 2015
TESTING TICKS
University of Maine Cooperative Extension Service
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Tick identification only
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Does not currently test tick specimens for diseases
November 2014: Maine voters approved a bond referendum
that will enable the building of a new lab for in-state disease
testing of tick specimens
After proper removal:
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Fill out the tick submission form from their website
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Place the tick to be identified in a crush proof container with
enough rubbing alcohol to cover the specimen; wrap in paper
towel and place in plastic bag  mail in the specimen
Alternatively, you can drop the tick off in-person
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UMaine Cooperative Extension: Insect Pests, Ticks and Plant Diseases. Available from: http://extension.umaine.edu/ipm/tickid/ Accessed August 17, 2015
LYME DISEASE IN THE NEWS
• “Maine legislature clears way for long-term Lyme disease
treatment” - Joe Lawlor, Portland Press Herald (June 2015)
• A bill to shield doctors from license sanctions for prescribing
long-term antibiotics becomes law without the governor’s
signature.
• “Maine records spike in diseases carried by ticks, not just
Lyme” – Jackie Farwell, Bangor Daily News (August 2014)
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• An emerging infection carried by the same ticks that
transmit Lyme disease has sickened a record number of
Mainers this year, according to the Maine Center for
Disease Control and Prevention. While rarely fatal,
anaplasmosis can cause serious illness if left untreated.
TICK-BORNE DISEASE
• Becoming a growing veterinary problem (dogs, horses, etc.)
• Support groups available
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For a list of support groups in Maine:
http://www.mainelyme.org/patient-support/support-groups/
• In addition to Lyme disease, ixodes ticks in the U.S. can
transmit:
Anaplasmosis
Babesiosis
Powassan virus
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ANAPLASMOSIS
• Human granulocytic anaplasmosis (HGA), a bacterial disease
Findings that may suggest coinfection (2.2 - 36% of ticks) with
B. burgdorferi include:
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Drug of choice: Doxycycline 100 mg BID x 10 days
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Leukopenia
Thrombocytopenia
High fever
Abnormal liver enzyme tests
14 days for coinfection with Lyme disease
94 confirmed cases in Maine in 2013
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First detected in Maine in mid 1990s
Lyme and Other Vector-borne Disease Information. Tick Borne Diseases. Maine Medical Center Research Institute. Available from:
http://www.mmcri.org/home/webSubContent.php?list=webcontentlive&id=107&catID=4&subCatID=19 Accessed 21 Aug 2015
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BABESIOSIS
• Parasitic disease caused by protozoa of Babesia genus
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Most commonly B. microti
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Invades red blood cells similar to the parasites that cause malaria
• Clinical manifestations mild to severe
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Fatigue, aches, fever, chills, sweating, dark urine, anemia
• Two major antimicrobial regimens (7-10 day treatment course)
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Atovaquone + Azithromycin or Quinine + Clindamycin
• 36 confirmed cases in Maine in 2013
First detected in a Maine tick in 2004
Lyme and Other Vector-borne Disease Information. Tick Borne Diseases. Maine Medical Center Research Institute. Available from:
http://www.mmcri.org/home/webSubContent.php?list=webcontentlive&id=107&catID=4&subCatID=19 Accessed 21 Aug 2015
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POWASSAN VIRUS
• Serious viral infection of the brain and surrounding tissues
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Fatal for 10-15% of patients
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Leaves ½ of its victims with permanent neurological damage
• Early signs and symptoms include:
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Headache, fever, nausea, vomiting, stiff neck, and sleepiness
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No delay between tick bite and transmission of the virus
• No specific treatment
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Hospitalization with supportive care
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Fatal, co-infected with Lyme disease and anaplasmosis
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5 total recorded cases in Maine, 60 in the U.S. over the past 10 years
Lyme and Other Vector-borne Disease Information. Tick Borne Diseases. Maine Medical Center Research Institute. Available from:
http://www.mmcri.org/home/webSubContent.php?list=webcontentlive&id=107&catID=4&subCatID=19 Accessed 21 Aug 2015
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• 1 confirmed case in Maine in 2013
SUMMARY
• Infected ticks can transmit Lyme disease to anyone
• Most common patient characteristics:
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Live in endemic areas
Ages 5 – 14 and 65+ years old
Males > Females
Spend ↑ amount of time outdoors in forested habitats
• Nymph and adult Ioxdes scapularis ticks transmit the disease
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Nymphs = 25% infected yet 90% of all cases
Transmission begins 36 hours after attachment
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• Most likely to have illness onset in June, July, or August
SUMMARY
• Diagnosed based on signs & symptoms and history of
possible tick exposure
• EM rash = pathognomonic sign
• Two-tiered testing using serodiagnostics
• Three phases of Lyme disease:
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• Early localized (days to weeks)
• Early disseminated (weeks to months)
• Late disease or chronic disseminated (months to years)
SUMMARY
• Prophylaxis should be given in select patients within 72 hours
after a tick bite
• Doxycycline 200 mg PO x 1 dose
• First-line medications for treatment include:
Doxycycline PO
Amoxicillin PO
Cefuroxime PO
Ceftriaxone IV
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Depends on patient characteristics, stage, & severity of disease
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