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Lyme Disease

Aka: Lyme Disease, Borrelia Burgdorferi, Lyme borreliosis

II. Epidemiology

  1. Incidence
    1. Most common tick borne disease in North America
    2. Cases in U.S. in 1994: 13,000
    3. Cases in U.S. in 1999: 16,000
    4. Cases in U.S. in 2006: 20,000
    5. Cases in U.S. in 2014: 19,985
    6. Annual Incidence in endemic areas: 0.5%
    7. Peak occurrence in North America: May to August
  2. Demographics
    1. Gender: Much more common in males
    2. Age: Bimodal peak distribution (ages 5-9 and 55-59 years old)
  3. Geographic areas involved
    1. Worldwide cases have occurred in Canada, Europe, Asia
    2. U.S. cases clustered in Northeast and Upper Midwest (90% of U.S. cases)
      1. High-Risk States
        1. Connecticut (Nantucket County: 1198 case/100,000)
        2. Delaware
        3. Maryland
        4. New Jersey
        5. New York
        6. Pennsylvania
        7. Rhode Island
        8. Wisconsin
      2. Moderate-Risk States
        1. Maine
        2. Massachusetts
        3. Minnesota
        4. New Hampshire
        5. Vermont
    3. Reference
      1. (1995) MMWR Morb Mortal Wkly Rep 44:459-62 [PubMed]
  4. Concurrent Lyme and Babesiosis is common (n=1156)
    1. Coinfection occurs 10% in southern New England
    2. Reference
      1. Krause (1996) JAMA 275:1657-60 [PubMed]

III. History

  1. 1975: Lyme Disease first reported in Lyme, Connecticut
    1. Cluster of new cases of Arthritis in children
  2. 1981: Borrelia Burgdorferi identified as cause

IV. Pathophysiology

  1. Borrelia Burgdorferi
    1. Causative Spirochete organism
    2. Carried by white tail deer
    3. Transmitted by Deer Ticks
    4. Natural reservoirs
      1. White-footed mouse and other small mammals
  2. Deer Ticks or Black Legged Tick
    1. Vectors for several infections
      1. Borrelia Burgdorferi (Lyme Disease)
      2. Babesia microti (Babesiosis)
      3. Anaplasma phagocytophila (causes HGA)
        1. Prior: Ehrilichia phagocytophila (Ehrlichiosis)
    2. Tick species
      1. Ixodes Scapularis
      2. Ixodes pacificus (West coast)
  3. Deer Ticks have two year life cycle:
    1. Egg to Larva
    2. Larva to Nymph
    3. Nymph to Adult
  4. In endemic areas:
    1. Nymphs infected: 12-30%
    2. Adult ticks infected: 28-65%
  5. Nymphs outnumber adult ticks 10:1
    1. Nymphs are responsible for 90% of Lyme Disease cases
    2. Transmission relies on the time it takes for Borrelia to migrate from tick midgut to its Salivary Glands
      1. Nymphs must attach for >36-48 hours for transmission
      2. Adult ticks must attach for >48-72 hours for transmission

V. Differential Diagnosis

  1. Erythema Migrans
    1. See Annular Lesion
    2. Cellulitis
    3. Tinea Corporis
    4. Granuloma Annulare
    5. Arthropod Bite reaction
      1. Usually <5 cm, painful, develops in minutes to hours
      2. Rash is often pruritic
      3. Resolves within 48 hours without viral symptoms
  2. Other Ixodes tick (Deer Tick) borne infection
    1. Babesiosis
    2. Human Granulocytic Anaplasmosis

VI. Signs and Symptoms: Stage 1 (Early localized disease)

  1. Less than 20% of people recall Tick Bite
  2. Localized Erythema Chronicum Migrans at Tick Bite site (present in 80% of cases)
    1. See Erythema Migrans
    2. Expanding red Macule or Papule
    3. Size 5 cm or greater (rapid and prolonged expansion is unique)
    4. Central clearing is variably present
  3. Mild constitutional Symptoms
    1. Fever (also consider HGA or Babesiosis)
    2. Malaise
    3. Arthralgias (esp. Monoarthritis of the knee or hip)
    4. Headache
    5. Neck stiff
    6. Other skin lesions

VII. Signs and Symptoms: Stage 2 (Early disseminated disease)

  1. Cardiac (<10% of patients; onset typically within 1-2 months of infection)
    1. Atrioventricular Block (49% with third degree AV Block)
    2. Pericarditis
    3. Myocarditis
  2. Musculoskeletal
    1. Arthralgias
    2. Myalgias
  3. Neurologic
    1. Bell's Palsy (or other Cranial NerveNeuropathy)
      1. Strongly consider empiric treatment for Lymes Disease with Bell's Palsy in Lyme endemic regions
    2. Lymphocytic Meningitis or Encephalitis
    3. Pseudotumor Cerebri
  4. Ophthalmologic
    1. Conjunctivitis
    2. Iritis
  5. Urologic
    1. Microscopic Hematuria
    2. Proteinuria
  6. Miscellaneous
    1. Regional Lymphadenopathy or General Lymphadenopathy
    2. Multiple Erythema Migrans lesions (hematogenous spread of infection)
    3. Hepatitis

VIII. Signs and Symptoms: Stage 3 (Late chronic disease)

  1. Large Joint Arthritis (especially knees; hips may also be involved)
    1. Occurs in 10-60% of untreated Lyme Disease
    2. Arthritis presents at approximately 6 months after infection onset
    3. Monoarticular or asymmetric Oligoarticular Arthritis
  2. Neurologic (10-15% of untreated patients)
    1. See Stage 2 neurologic conditions
    2. Symptoms
      1. Altered Mental Status
      2. Headaches
      3. Neck Pain or stiffness
      4. Sudden Hearing Loss
    3. Classic triad
      1. Lymphocytic Meningitis
      2. Cranial Neuropathy (especially Bell's Palsy)
      3. Radiculoneuropathy
    4. Other manifestations
      1. Subacute encephalopathy
      2. Axonal Polyneuropathy
      3. Leukoencephalopathy
      4. Cerebellar Ataxia
      5. Mononeuritis multiplex

IX. Labs: Two tiered protocol

  1. See Lyme Test
  2. Lyme Titer (ELISA) - first tier testing
    1. Not needed if Erythema Migrans in endemic areas
    2. False Positive Rate is high
    3. Positive results are reflexed to Western Blot for confirmation
  3. Lyme Western Blot
    1. Confirms Lyme Titer result

X. Labs: Other

  1. Synovial Fluid Lyme PCR
    1. Joint aspiration in cases of suspected Lyme Arthritis
  2. Cerebrospinal fluid (CSF) for Intrathecal Lyme Antibody production
    1. Indicated for neurologic symptoms
  3. C6 Peptide assay (IgG enzyme linked immunosorbent assay)
    1. Under study as of 2012 for replacement of the two tiered protocol

XI. Labs: Precautions

  1. Lyme urine antigen
    1. High False Positive Rate and not recommended
  2. Borrelia Burgdorferi IgG and IgM
    1. Persists for years following effective antibiotic treatment
    2. Positive test after treatment does not indicate failed antibiotics or chronic infection

XII. Labs: Tests to identify other causes

  1. Erythrocyte Sedimentation Rate (ESR) elevated
  2. Complete Blood Count (CBC)
    1. Leukocytosis
    2. Anemia
  3. Antinuclear Antibody (ANA) negative
  4. Rheumatoid Factor (RF) negative

XIII. Precautions

  1. Consider Lyme Disease in unexplained symptoms (Arthralgias, focal weakness) despite lack of bite history
    1. Fluctuating meningoencephalitis symptoms
    2. Cranial Nerve palsy (e.g. Bell's Palsy, especially if bilateral)
    3. Peripheral Neuropathy or radiculopathy
    4. New first-degree AV Block or dysrhythmia
    5. New left-ventricular dysfunction
  2. Information based on IDSA and CDC guidelines
    1. IDSA: Infectious Disease Society of America
    2. IDSA is considered standard of care recommendations
    3. Tertiary centers (e.g. Mayo) follow these guidelines
  3. Other guidelines (e.g. ILADS) are not reviewed here
    1. ILADS: International Lyme and Associated Diseases
    2. ILADS guidelines are considered controversial

XIV. Management: Deer Tick Bite

  1. See Deer Tick Bite (includes antibiotic prophylaxis)

XV. Management: Stage 1 (Early Lyme Disease and Erythema Migrans)

  1. Treatments risks Jarisch-Herxheimer type reaction
    1. Borrelia is a Spirochete with potential for similar reaction to antibiotics as for Syphilis
  2. Doxycycline (Avoid in pregnancy and under age 9 years)
    1. Preferred oral agent due to cross-coverage of other tick-borne infections
    2. Adult: 100 mg orally twice daily for 10 to 21 days (typically 14 days per CDC)
    3. Child (age >8): 4 mg/kg orally divided twice daily (max 100 mg/dose) for 10-21 days (typically 14 days per CDC)
  3. Amoxicillin
    1. Adult: 500 mg orally three times daily for 14 to 21 days (typically 21 days per CDC)
    2. Child: 50 mg/kg/day divided three times daily (max 500 mg/dose) for 14 to 21 days (typically 21 days per CDC)
  4. Cefuroxime (Ceftin)
    1. Adult: 500 mg orally twice daily for 14 to 21 days
    2. Child: 30 mg/kg/day divided twice daily (max: 500 mg/dose) for 14 to 21 days
  5. Macrolides have lower efficacy (consider other agents above if possible)
    1. Use only if allergic to above agents
    2. Azithromycin
      1. Adult: 500 mg daily for 10 days
      2. Child: 10 mg/kg daily for 10 days
    3. Clarithromycin
      1. Adult: 500 mg orally twice daily for 21 days
      2. Child: 7.5 mg/kg (max: 500 mg/dose) orally twice daily for 21 days
    4. Erythromycin
      1. Adult: 500 mg orally four times daily for 21 days
      2. Child: 12.5 mg/kg (max 500 mg/dose) orally four times daily for 21 days
  6. If suspect Cellulitis versus Erythema Migrans
    1. Augmentin 50 mg/kg/day divided bid or tid (up to 875 mg twice daily)
    2. Cefuroxime 30 mg/kg/day divided twice daily (up to 500 mg twice daily)
    3. Doxycycline 4 mg/kg divided twice daily (up to 100 mg twice daily)
  7. Antibiotics to avoid (not indicated)
    1. Avoid First Generation Cephalosporins (Cephalexin)
    2. Avoid Fluoroquinolones
    3. Avoid Septra, Metronidazole, Penicillin G

XVI. Management: Stage 2 (Early disseminated with cardiac or neurologic findings)

  1. Indications for hospitalization
    1. New first degree AV Block with PR >300 ms
    2. New second or third degree AV Block
    3. Chest Pain, Syncope or Dyspnea
    4. Lyme Meningitis
  2. Protocol
    1. Isolated Bell's Palsy may be treated with agents used for stage 1 - Erythema Migrans findings as above
    2. Obtain Lumbar Puncture for neurologic findings attributed to Lymes Disease
  3. Ceftriaxone (Rocephin)
    1. Adult: 2g/day IV for 14 to 21 days
    2. Child: 75-100 mg/kg/day IV for 14 to 21 days
  4. Cefotaxime (Claforan)
    1. Adult: 2g every 8 hours for 14 to 21 days
    2. Child: 150-200 mg/kg/day divided every 6 to 8 hours IV for 14-21 days
  5. Doxycycline (Avoid in pregnancy and under age 9 years)
    1. Adult: 200 to 400 mg orally divided twice daily for 10 to 28 days
    2. Child: 4 to 8 mg/kg orally divided twice daily for 10 to 28 days

XVII. Management: Stage 3 (Late Lyme Disease)

  1. Arthritis
    1. Use same oral antibiotic protocols as under Stage 1 - Erythema Migrans management
    2. Persistent or recurrent Joint Swelling despite initial antibiotics course
      1. Consider repeating a 4 week course of oral antibiotics or 2-4 week course of Ceftriaxone
  2. Neurologic findings
    1. Use same intravenous antibiotic protocols as under Stage 2 - early disseminated management
    2. Post-Lyme Disease syndrome of persistent Fatigue or cognitive difficulties
      1. No benefit to prolonged antibiotic courses or other medication management
      2. Klempner (2013) Am J Med 126(8):665-9 +PMID:23764268 [PubMed]

XVIII. Prevention

  1. See Prevention of Vector-borne Infection
  2. Lyme Vaccine (No longer available in U.S.)
  3. Insecticide
    1. Acaricide applied to residential areas in mid May
    2. Provides 97% protection during peak nymph activity

XIX. Resources

  1. IDSA Guidelines
    1. http://www.journals.uchicago.edu/IDSA/guidelines/

XX. Reference

  1. Hensley and Swaminathan in Herbert (2016) EM:Rap 16(7): 7-9
  2. Steere in Mandell (2000) Infectious Disease, p. 2504-14
  3. (2000) Med Lett Drugs Ther 42(1077): 37 [PubMed]
  4. (1997) Med Lett Drugs Ther 39(1000) [PubMed]
  5. Fix (1998) JAMA 279(3): 206-10 [PubMed]
  6. Rahn (1998) Postgrad Med 103(5):51-70 [PubMed]
  7. Still (1997) Postgrad Med 102(1):65-72 [PubMed]
  8. Verdon (1997) Am Fam Physician, 56(1): 427-436 [PubMed]
  9. Nadelman (1995) Am J Med 98:15S-24S [PubMed]
  10. Stanek (2003) Lancet 362:1639-47 [PubMed]
  11. Wormser (2006) Clin Infect Dis 43(9):1089-134 [PubMed]
  12. Wright (2012) Am Fam Physician 85(11): 1086-93 [PubMed]

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Ontology: Borrelia burgdorferi (C0006034)

Definition (NCI_CDISC) Any bacterial organism that can be assigned to the species Borrelia burgdorferi.
Definition (NCI) A species of bacteria within the phylum Spirochaetes that is the causative agent of Lyme disease.
Definition (MSH) A specific species of bacteria, part of the BORRELIA BURGDORFERI GROUP, whose common name is Lyme disease spirochete.
Concepts Bacterium (T007)
MSH D025065
SnomedCT 76327009
LNC LP14087-8, MTHU002753
English Borrelia burgdorferi, Borrelia burgdorferi Johnson et al. 1984 emend. Baranton et al. 1992, borrelia burgdorferi, lyme disease spirochete, Borrelia burgdorferi sensu stricto, Lyme Disease Spirochete, BORRELIA BURGDORFERI, Borrelia burgdorferi (organism)
Swedish Borrelia burgdorferi
Czech Borrelia burgdorferi sensu stricto, Borrelia burgdorferi
Finnish Borrelia burgdorferi
Italian Malattia di Lyme da spirochete, Borrelia burgdorferi sensu stricto, Borrelia burgdorferi
Russian LAIMA BOLEZNI SPIROKHETA, BORRELIA BURGDORFERI, Л�ЙМ� БОЛЕЗ�И СПИРОХЕТ�
Croatian BORELIJA BURGDORFERI
Polish Borrelia burgdorferi
Japanese ライム病ボレリア, ボレリア･ブルグドルフェリ
Portuguese Espiroqueta da Doença de Lyme, Borrelia burgdorferi, Borrelia burgdorferi sensu stricto, Espiroqueta Causadora da Doença de Lyme
Spanish Borrelia burgdorferi (organismo), Borrelia burgdorferi, Borrelia burgdorferi sensu stricto, Espiroqueta de la Enfermedad de Lyme
French Borrelia burgdorferi, Borrelia burgdorferi sensu stricto, Spirochète de la maladie de Lyme
German Borrelia burgdorferi, Borrelia burgdorferi sensu stricto
Dutch Borrelia burgdorferi, Borrelia burgdorferi sensiu stricto, Spirocheet ziekte van Lyme
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Lyme Disease (C0024198)

Definition (MEDLINEPLUS)

Lyme disease is a bacterial infection you get from the bite of an infected tick. The first symptom is usually a rash, which may look like a bull's eye. As the infection spreads, you may have

  • A fever
  • A headache
  • Muscle and joint aches
  • A stiff neck
  • Fatigue

Lyme disease can be hard to diagnose because you may not have noticed a tick bite. Also, many of its symptoms are like those of the flu and other diseases. In the early stages, your health care provider will look at your symptoms and medical history, to figure out whether you have Lyme disease. Lab tests may help at this stage, but may not always give a clear answer. In the later stages of the disease, a different lab test can confirm whether you have it.

Antibiotics can cure most cases of Lyme disease. The sooner treatment begins, the quicker and more complete the recovery.

After treatment, some patients may still have muscle or joint aches and nervous system symptoms. This is called post-Lyme disease syndrome (PLDS). Long-term antibiotics have not been shown to help with PLDS. However, there are ways to help with the symptoms of PLDS, and most patients do get better with time.

NIH: National Institute of Allergy and Infectious Diseases
Definition (NCI) An infectious disease caused by the spirochete Borrelia burgdorferi. Early manifestations of infection may include fever, headache, fatigue, depression, and a characteristic skin rash called erythema migrans. Left untreated, late manifestations involving the joints, heart, and nervous system can occur.
Definition (MSH) An infectious disease caused by a spirochete, BORRELIA BURGDORFERI, which is transmitted chiefly by Ixodes dammini (see IXODES) and pacificus ticks in the United States and Ixodes ricinis (see IXODES) in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. The disease was formerly known as Lyme arthritis and first discovered at Old Lyme, Connecticut.
Definition (CSP) recurrent multisystemic infectious disease caused by a spirochete, Borrelia burgdorferi, which is transmitted chiefly by Ixodes ticks; it is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations.
Concepts Disease or Syndrome (T047)
MSH D008193
ICD9 088.81
ICD10 A69.2 , A69.20
SnomedCT 23502006, 154376000
LNC LA10487-9
English Borreliosis, Lyme, Lyme Borreliosis, Disease, Lyme, LYME DISEASE, LYME DIS, Borrelia burgdorferi infection, lyme disease (diagnosis), Lyme's disease, Lymes disease, Borrelia Burgdorferi Infection, Borrelia, Lyme disease, unspecified, Lyme Disease [Disease/Finding], lyme borreliosis, lyme's disease, Disease;lyme, lymes disease, borrelia burgdorferi infection, Infection due to Borrelia burgdorferi sensu lato, Infection by Borrelia burgdorferi, Lyme disease, Lyme borreliosis, Steere's disease, Lyme disease (disorder), Lyme; disease, disease (or disorder); Lyme (disease), disease; Lyme, Lyme Disease, lyme disease
Swedish Lyme-sjukdom
Japanese ﾗｲﾑﾋﾞｮｳ, ﾗｲﾑﾎﾞﾚﾘｱｼｮｳ, ﾎﾞﾚﾘｱﾌﾞﾙｸﾞﾄﾞﾙﾌｪﾘｶ�ｾ�, ライム・ボレリア症, ボレリア・ブルグドルフェリ感染, ライム･ボレリア症, Lymeボレリア症, ライム関節炎, Lyme病, ライム病
Czech lymeská borelióza, lymská nemoc, lymeská nemoc, Lymská choroba, Lymská borelióza, Lymeská borrelióza, Lymeská choroba, Infekce vyvolaná Borrelia burgdorferi, borelióza, lymeská borrelióza, borrelióza, lymská borelióza
Spanish Infección por Borrelia burgdorferi, enfermedad de Lyme (trastorno), enfermedad de Lyme, infección por Borrelia burgdorferi, Enfermedad de Lyme, Borreliosis de Lyme
French Infection à Borrelia burgdorferi, Maladie de Lyme, Borréliose de Lyme
Dutch Borrelia burgdorferi-infectie, Lyme; disease, aandoening; Lyme (disease), disease; Lyme, ziekte van Lyme, Lyme-borreliose, Lyme-ziekte, Ziekte, Lyme-
Portuguese Infecção a Borrelia burgdorferi, Borreliose de Lyme, Doença de Lyme
German Borrelia burgdorferi-Infektion, Lyme-Borreliose, Lyme-Krankheit
Italian Borreliosi di Lyme, Infezione da Borrelia burgdorferi, Borelliosi di Lyme, Malattia di Lyme
Finnish Lymen borrelioosi
Russian LAIMSKAIA BOLEZN', LAIMA BOLEZN', Л�ЙМ� БОЛЕЗ�Ь, Л�ЙМСК�Я БОЛЕЗ�Ь
Korean �임병
Croatian LYMSKA BOLEST
Polish Krętkowica kleszczowa, Choroba z Lyme, Borelioza z Lyme
Hungarian Lyme-betegség, Lyme borreliosis, Lyme betegség, Lyme-kór, Borrelia burgdorferi fertőzés
Norwegian Lyme-sykdom, Lyme-borreliose
Derived from the NIH UMLS (Unified Medical Language System)

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