EM@3AM: Lyme Disease

A 35-year-old male presents for intermittent fevers, abdominal pain, and headaches for 3 weeks. On further questioning, he also states he has arthralgias. He denies other medical problems.  Review of systems is remarkable for a recent camping trip in the Boundary Waters Canoe Area of Minnesota.

Triage vital signs (VS): BP 135/65, HR 82, T 100.8F oral, RR 16, SpO2 98% on room air.

Pertinent physical examination findings: HEENT, pulmonary, and cardiac exams normal. Mild hepatomegaly noted. Full ROM in all extremities, but with mild tenderness in knees bilaterally without effusion. You see a bulls-eye rash >5 cm on trunk.

What’s the next step in your evaluation and treatment?

Answer: Lyme Disease, Borreliosis^1-17

• Epidemiology:
  • The bite of the deer tick, Ixodes scapulari, serves as a vector for transmission of Borrelia burgdorferi, the spirochete which causes Lyme Disease.¹
  • Spread of I. scapularis has progressed as far south as Texas and as far north as Canada. It has also been reported in Europe, China, Japan, and Australia.¹
  • 95% cases reported originate in a conglomeration of 13 states in NE and upper Midwest.¹
  • 4 million tests associated with Lyme Disease are performed each year, costing ~$500 million.²
  • In 2016, 26,203 cases were reported with an incidence of 8.1 cases/100,000 people.³
  • Additional risk factors include surgical or functional asplenia (e.g. sickle cell disease), bimodal distribution of age, and an immune compromised state.

• Clinical Presentation:
  • S/p tick exposure—Ask the patient if the tick was engorged and recent travel or living in a Lyme endemic area.
  • Unfortunately, a significant number of patients are not aware of or do not recall a tick bite.
  • Early and nonspecific symptoms: fever, malaise, fatigue, arthralgias.
  • Late symptoms: headache, lethargy and irritability, sleep disturbances, syncope, chest pain, dyspnea.
  • Mimicking infection of B. miyamotoi; employs same vector and geographically widespread.
    • Notable differentiators: absence of rash, elevated LAEs (75%), thrombocytopenia (60%), and leukopenia (51%).⁸
• Evaluation:
  • Assess ABCs and VS—may show fever. If late and severe, can see tachypnea due to dyspnea.
  • Perform a complete physical examination:
    • HEENT: Scleral icterus
    • Neuro: CN VII palsies
    • Abdominal: hepatomegaly
    • Integumentary/MSK: Erythema migrans, arthralgias
  •  Laboratory evaluation: CBC, CMP, ECG
    • Lyme Serology⁴
      • Do not test people unlikely to have disease!
        • Low incidence generates very low PPV.⁹
      • Erythema migrans + endemic area = treat without testing.
      • 1^st tier—Enzyme Immunoassay (EIA) quantifies antibodies vs Borrelia burgdorferi.
        • If positive or equivocal, then progress to 2^nd tier.⁴
      • 2^nd tier—Immunoblot against more specific surface proteins on B. burgdorferi.⁴
      • When infection localized, testing sensitivity is < 40%.^5-6
      • After systemic immune response mounts, sensitivity in disseminated infections is 70-100% and specificity of 98-100%.^5-6
      • Providers are not particularly skilled at this interpretation, with 42.4% of providers misinterpreting results of an immunoblot in a Lyme endemic area.⁷
      • If Sx>30 days, + Immunoblot required for diagnosis of Lyme Disease
      • Other immunologic tests or band cut offs are not recommended due to lack of validation.
        • PCR demonstrates low sensitivity with brief window of spirotchetemia, but it can be useful in specific specimens e.g. CSF, skin bx.¹⁰
      • IgM and IgG serologies persist for many years and are thus not useful markers of treatment efficacy.⁴
• Treatment: 2006 IDSA Guidelines¹¹
  • Prophylaxis: Must satisfy ALL of the 3 following criteria
    • Ixodes scapularis latched > 36 hours/engorged
    • Lyme endemic area
    • Seek tx within 72 hours of bite
      • Doxycycline 200 mg PO x 1
        • NNTB=12
  • Early Lyme: Doxycycline 100 mg BID x 10 days¹² or Amoxicillin 500 mg TID x 14 days.
    • • Data do not show preference of one antibiotic.¹³
    • In a meta-analysis assessing toxicity and efficacy of PO antibiotics in early Lyme with erythema migrans, PCNs generated a superior treatment response in comparison to macrolides and tetracyclines, have a more favorable side effect profile vs tetracyclines and cephalosporins, and were equally effective in preventing dissemination of Lyme Disease.¹⁴
  • Early Disseminated Lyme:
    • Meningoencephalitis: Ceftriaxone 2g IV qd x 14 days orPCN G 4 million U IV q4hr x 14 days.
    • CN Palsies: Doxycycline 100 mg BID x 10 days orAmoxicillin 500 mg TID x 14 days.
    • Carditis:
      • Mild: 1° AV block, PR<300 ms: Doxycycline 100 mg BID x 30 days orAmoxicillin 500 mg TID x 30 days.
      • Severe: Aymptomatic, 2° or 3° AV block: Ceftriaxone 2g IV qd x 14 days orPCN G 4 million U IV q4hr x 14 days.
  • Late Lyme:
    • Arthritis: Doxycycline 100 mg BID x 30 days orAmoxicillin 500 mg TID x 30 days.
      • Escalate to ceftriaxone and PCN IV if fail enteral ABTX.
    • Encephalomyelitis, peripheral neuropathy, encephalopathy: Ceftriaxone 2g IV qd x 14 days.
•  Disposition:
  • Early Lyme: Discharge home with follow up.
  • Early Disseminated Lyme: Carditis and meningoencephalitis admitted; telemetry indicated for any conduction abnormalities.
  • Late Lyme: Admission to ICU for rare cases of encephalomyelitis and encephalopathy.

• Pearls:
  • Due to spirochetemia, SIRS response after initiating antibiotics may be seen (Jarisch Harxheimer reaction).
  • Use PO antibiotics first, as long term, serious adverse outcomes are the result of unnecessarily protracted IV antibiotic use.¹⁵
  • If parenteral antibiotics are necessary, ceftriaxone is recommended.¹⁶
  • Concern for teeth staining in children in tetracycline use does not occur with doxycycline.¹⁷

From Dr. Katy Hanson at Hanson’s Anatomy:

A 45-year-old man presents to the emergency department worried about a tick bite. He indicates he just arrived home from Connecticut and on the airplane he noticed a tick on his leg. He denies any symptoms. He denies hiking and camping. He was visiting his grandmother and only notes that he was outside gardening with her two days ago. He is very concerned about Lyme disease because he has read about it in the newspaper. Upon examination you find what appears to be an engorged Ixodes tick attached to the patient’s lower left leg. No rash is noticeable. What is the most appropriate management of this tick bite?

A) Carefully remove the tick and discharge

B) Carefully remove the tick and perform serologic IgM and IgG antibody testing for Borrelia burgdorferi

C) Carefully remove the tick and send it for testing to determine if it is infected with Borrelia burgdorferi

D) Carefully remove the tick and treat with doxycycline before discharge

Answer: D

Lyme disease is the most common tick-borne illness in the United States and is caused by the spirochete Borrelia burgdorferi. Individuals at highest risk for Lyme disease are those who live in endemic regions and have occupational or recreational exposure to ticks. However, in highly endemic regions people may even be at risk in their yards. The factors affecting transmission of Lyme disease include whether the tick was of the Ixodes species, if the tick attached, how long the tick was attached and if it was engorged. Ticks found walking on the skin or ticks that are easily removed are not attached and hence will not transmit disease. The duration of tick attachment is important because B. burgdorferi are rarely transmitted within the first 48 hours of attachment. If a tick is bigger or engorged then that means it has been feeding and is more likely to have transmitted disease. When a tick is detected, the first step is carefully removing the tick without squeezing or crushing it so as to not spill contents of the tick into the wound. The Infectious Disease Society of America recommends antibiotic prophylaxis if patients meet ALL of the following criteria: The attached tick is identified as an Ixodes scapularis tick; the tick is estimated to have been attached for greater than 36 hours (based on known exposure or degree of engorgement); prophylaxis is begun within 72 hours of tick removal; greater than 20% local rate of infection of ticks with B. burgdorferi (part of New England and mid Atlantic states, Wisconsin and Minnesota); and doxycycline is not contraindicated. Based on the degree of engorgement by an Ixodes tick, and considering the high rate of infection of ticks in New York, the patient in this question meets these criteria and should be treated appropriately with doxycycline.

Carefully removing the tick and discharging (A) is incorrect as the patient in this question is at a higher risk for infection with Borrelia burgdorferi based on the Infectious Disease Society of America recommendations. Carefully removing the tick and performing serologic IgM and IgG antibody testing for Borrelia burgdorferi (B) would not be appropriate because antibodies to the spirochete have not appeared yet. Thus, you should not obtain serologic testing with the aim of making a new diagnosis at the time of the tick bite. Carefully removing the tick and sending it for testing to determine if it is infected with Borrelia burgdorferi (C) is also not recommended since the results will not affect clinical management. A tick infected with B. burgdorferi may not necessarily transmit disease unless it has been feeding for greater than 36 hours. If the tick has been attached for greater than 36 hours then prophylaxis is recommended whether the tick is infected or not.

Rosh Review Free Qbank Access

References:

1. Tintinalli’s Emergency Medicine: A Comprehensive Review. Chapter 160 Zoonotic Infections
2. Hinckley AF, Connally NP, Meek JI, et al. Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis. 2014;59(5):676-681.
3. Centers for Disease Control and Prevention.Lyme disease: data and statistics. https://www.cdc.gov/lyme/stats/index.html.Accessed October 28, 2018.
4. Lantos PM, Auwaerter PG, Nelson CA. Lyme Disease Serology. JAMA. 2016;315(16):1780-1781.
5. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509.
6. Molins CR, Sexton C, Young JW, et al. Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation.J Clin Microbiol. 2014;52(10):3755-3762.
7. Conant JL, Powers J, Sharp G, Mead PS, Nelson CA. Lyme Disease Testing in a High-Incidence State: Clinical Knowledge and Patterns. Am J Clin Pathol. 2018; 149(3):234-240.
8. Molloy PJ, Telford SR III, Chowdri HR, et al. Borrelia miyamotoi disease in the northeastern United States: a case series. Ann Intern Med. 2015; 163(2):91-98.
9. Lantos PM, Branda JA, Boggan JC, et al. Poor positive predictive value of Lyme disease serologic testing in an area of low disease incidence. Clin Infect Dis. 2015;61(9):1374-1380.
10. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509.
11. IDSA Guidelines: Wormser GP et al. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. 2006. Clin Inf Dis. 43(9): 1089-1134.
12. Committee on Infectious Diseases, American Academy of Pediatrics. Red Book, 2018-2021: Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics; 2018:905.
13. Shapiro ED, Wormser GP. Lyme Disease in 2018: What is new (and What is Not). JAMA. 2018;320(7):635-636.
14. Han JM, Meissner HC, Osani M, Moubary F, Freund K, Bannuru R. Comparative effectiveness and toxicity of oral antibiotics for early Lyme disease associated with erythema migrans: a systematic review and network meta-analysis. ECCMID 2017.
15. 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.
16. Sanchez E, Vannier E, Wormser GP. Diagnoses, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A review. JAMA. 2016;315(16):1767-1777.
17. Todd S et al. No Visible Dental Staining in Children Treated with Doxycycline for Suspected Rocky Mountain Spotted Fever.

FOAMed

1. https://emergencymedicinecases.com/video/lyme-disease-101/
2. http://www.emdocs.net/lyme-disease-ed-presentations-management-pearls-pitfalls/
3. https://pedemmorsels.com/pediatric-lyme-disease/
4. https://wikem.org/wiki/Lyme_disease
5. http://foamcast.org/2018/09/27/lyme-borreliosis/