British Columbia Drug and Poison Information Centre (BC DPIC)

By Dorothy Li, B.Sc. (Pharm.), R.Ph., CSPI, Drug and Poison Information Pharmacist, BC Drug and Poison Information Centre
Reviewed by C. Laird Birmingham, MD, M.H.Sc., FRCPC, Muhammad Morshed, PhD, SCCM and William R. Bowie, MD, FRCPC.

Lyme disease (LD) in North America is caused by the bacterium Borrelia burgdorferi (Bb). Bb is transmitted in BC by Ixodes pacificus and I. angustus, a blacklegged tick found in valley regions of Vancouver Island, Lower Mainland, Sunshine Coast and the Interior. The most common tick found on humans in BC (wood or dog tick) does not carry Bb. In the rest of Canada (east of the Rockies) Bb is transmitted by I. scapularis. Reports of LD in Canada quadrupled between 2009 and 2013, likely due to the spread of ticks in eastern Canada as a result of climate change. The risk of LD in BC is low. Tick infection rates in BC have remained stable and low (<1%) compared to >20% in Northeastern United States.^1-11

LD has three accepted clinical stages (Table 1). Early localized LD peaks in June to August and presents with an oval or round expanding rash (> 5 cm) at the bite site, called erythema migrans (EM). EM is mostly homogenous; less than 10% has a bull's-eye appearance.^1,12-13 Differential diagnosis includes a bacterial infection at the bite site or a hypersensitivity reaction to tick saliva at the bite site usually within 48 hours, less than 5 cm in diameter and resolving within 48 hours.^12-13

Disseminated LD is diagnosed by antibody testing. It takes approximately two to four weeks for antibody testing to become positive and may be influenced by prior antibiotic treatment. Antibodies remain high for many years so a positive test can indicate recent or remote infection.^7,10,14-18

Prophylaxis

Removing a tick within 36 hours of attachment (time required for Bb to move from the blacklegged tick gut to it's salivary glands) minimizes risk of LD. A single dose of doxycycline is 87% effective in preventing LD post-tick bite in areas of high tick Bb infection rates. Prophylaxis following tick bite in BC is not recommended due to low tick Bb infection rates (<1%).^7,19-21

Treatment

The Public Health Agency of Canada recommendations follow the Infectious Disease Society of America (IDSA) guidelines.²² The International Lyme and Associated Diseases Society (ILADS) recommend a longer course of antibiotics. Both recommend early treatment of acute localized LD because over 80% of patients treated for early LD have long-term complete resolution of symptoms.^2,19,22-27 The IDSA recommends oral doxycycline, amoxicillin or cefuroxime axetil as first line and oral macrolides as second line treatment. Parenteral ceftriaxone, penicillin G or cefotaxime are recommended for meningitis, arthritis with neurologic symptoms or treatment-resistant arthritis. Length of treatment depends on LD stage (14-28 days).¹⁹ If antibody testing is indicated, patients should have samples drawn for testing prior to starting antibiotics.

Chronic Lyme disease

The existence of chronic LD remains controversial^19,28-29, but there is no compelling evidence that it is due to active or previous infection with Bb. ^18,19,30-31 Symptoms reported include fatigue, arthralgias, melalgias, paresthesias, insomnia and cognitive impairment.^29,31 Post-treatment Lyme disease syndrome (PTLDS) is further differentiated from chronic LD where the former refers to symptoms that persist after antibiotic treatment for LD.³² The incidence of fatigue, cognitive impairment, insomnia, joint pain and numbness in chronic LD is increased in some studies, while others report no difference from controls.^24,33-34 Four small and one moderate-sized randomized controlled trials reported little or no benefit of long-course antibiotics for fatigue, pain or neurocognitive function in PTLDS.^35-38 The IDSA recommends symptomatic therapy (not antibiotics)¹⁹, whereas the ILADS recommends "considering" antibiotics with probiotics in patients with persistent symptoms of LD including using "higher doses, longer durations or combinations of first-line agents," though this is based on expert opinion only.²³ Some clinicians recommend adding metronidazole to the regimen to disrupt the 'cystic form' of Bb, despite no evidence of benefit or the existence of Bb cysts in humans.^23,30,39

Alternative treatments

There is no evidence for any of the following adjunctive therapies for LD: methyl B 12 injections, Myers infusions (intravenous nutrient therapy), ribose powder, andrographis, eleuthero, glutathione, vitamin C, coenzyme Q10, alpha lipoic acid, vitamin B complex, vitamin B6, magnesium, omega-3, omega-6, and NT-factor.

Despite the controversy among various groups and guidelines, all emphasize careful differential diagnosis and evaluation for other causes.^19,23,39 At the BC Women's Hospital and Health Centre, a Complex Chronic Diseases Program has been set up to provide care for patients with chronic LD as well as other pain syndromes. Patients with symptoms compatible with chronic LD sometimes suffer for years, through countless clinical evaluations and tests without a proper diagnosis and effective treatment.^40,41 It's important that pharmacists understand the risks of contracting LD and the controversies concerning diagnosis, prophylaxis and treatment so that they can help patients navigate through the conflicting information.

Table 1: Stages of LD: ^{7,12,17,19-20,34,42-44}

This article was published in British Columbia Pharmacy Association (BCPhA)'s The Tablet. 2016 Sep/Oct: 10-11.    

References:

1. Government of Canada [Internet]. Ottawa (ON): Government of Canada; National Lyme Disease Surveillance in Canada 2013: Web Report. Feb 09, 2015. [cited July 16, 2015]. Available from: http://healthycanadians.gc.ca/publications/diseases-conditions-maladies-affections/2009-2012-lyme/index-eng.php.

2. Ogden NH, Lindsay LR, Morshed M, Sockett PN, Artsob H. The emergence of Lyme disease in Canada. CMAJ. 2009:180(12): 1221-1224.

3. Public Heatlh Agency of Canada [Internet]. Ottawa (ON): Public Health Agency of Canada. Ogden NH, Lindsay LR, Morshed M, Sockett PN, Artsob H. The rising challenge of Lyme borreliosis in Canada. Canada Communicable Disease report. 2008;34(1). [cited July 18, 2016]. Available from: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08vol34/dr-rm3401a-eng.php.

4. Niagra Region [Internet]. Thorold (ON): Niagrara Region; Ticks and Lyme Disease. [cited July 18, 2016]. Available from: www.niagararegion.ca/living/health_wellness/disease-prevent/lyme-disease.aspx.

5. Public Health Agency of Canada [Internet]. Ottawa (ON): Public Health Agency of Canada. Ogden NH, Koffi JK, Pelcat Y, Lindsay LR. Environmental risk from Lyme disease in central and eastern Canada: a summary of recent surveillance information. CCDR: Volume 40-5, March 6, 2014. [cited July 19, 2016]. Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/14vol40/dr-rm40-05/dr-rm40-05-1-eng.php#footnote6.

6. Government of Canada [Internet]. Ottawa (ON): Government of Canada. Surveillance of Lyme Disease. Date modified: July 15, 2016. [cited July 16, 2016]. Available at: http://healthycanadians.gc.ca/diseases-conditions-maladies-affections/disease-maladie/lyme/surveillance-eng.php.

7. Henry B, Morshed M. Lyme disease in British Columbia: Are we really missing an epidemic? BCMJ. 2011;53(5):224-229.

8. Mak S, Morshed M, Henry B. Ecological Niche Modeling of Lyme Disease in British Columbia, Canada. J Med Entomology. 2010;47(1):99-105.

9. Hu LT. Lyme Disease. Ann Int Med. 2016;164(9):ITC65-ITC80.

10. Government of Manitoba [Internet]. Winnipeg (MB): Government of Manitoba. Lyme Disease (Lyme Borreliosis). February 10, 2013. [cited July 9, 2020]. Available at: http://www.gov.mb.ca/health/publichealth/cdc/protocol/lyme.pdf.

11. Morshed MG, Lee MK, Man S, Fernando K, Wong Q, Hojgaard A, et al. Surveillance for Borrelia burgdorferi in Ixodes ticks and small rodents in British Columbia. Vector-Borne Zoonotic Diseases. 2015;15(11):701-705.

12. Godar DA, Laniosz V, Wetter DA. Lyme Disease update for the general dermatologist. Am J Clin Dermatol. 2015;16:5-18.

13. Nadelman RB. Erythema Migrans. Infect Dis Clin North Am. 2015;29:211-239.

14. Public Health Agency of Canada. [Internet]. Ottawa (ON): Public Health Agency of Canada. Lindsay LR, Bernat K, Dibernardo A. Laboratory diagnostics for Lyme Disease. CCDR: 40-11, May 29, 2014. [cited June 10, 2016]. Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/14vol40/dr-rm40-11/dr-rm40-11-lyme-2-eng.php.

15. Kling R, Galanis E, Morshed M, Patrick DM. Diagnostic testing for Lyme disease: beware of false positives. BCMJ. 2015;57(9):396,399.

16. Tevaarwerk G. Re: Diagnostic testing for Lyme Disease. [Letter]. BCMJ. 2016;58(1):9.

17. Shapiro ED. Lyme Disease. N Eng J Med. 2014;370(18):1724-1731.

18. Halperin JJ. Chronic Lyme disease: misconceptions and challenges for patient management. Infection Drug Resistance. 2015;8:119-128.

19. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Kelmpner MS, 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. CID. 2006;43:1089-1134.

20. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet. 2012;379:461-73.

21. Public Health Agency of Canada. [Internet]. Ottawa (ON):  Public Health Agency of Canada. Hatchette TF, Davis I, Johnston BL. Lyme disease: clinical diagnosis and treatment. CCDR: Volume 40-11, May 29, 2014. [cited May 2, 2016]. Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/14vol40/dr-rm40-11/assets/pdf/14vol40_11-eng.pdf.

22. Government of Canada. [Internet]. Ottawa (ON): Government of Canada. For health professionals: Lyme disease. August 2, 2016. [cited  August 22, 2016]. Available at: http://www.healthycanadians.gc.ca/diseases-conditions-maladies-affections/disease-maladie/lyme/professionals-professionnels/index-eng.php#a5.

23. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical managmenet of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103-1135.

24. Seltzer EG, Gerber MA, Cartter ML, Freudigman K, Shapiro ED. Long-term outcomes of persons with Lyme Disease. JAMA. 2000;283:609-616.

25. Chaaya G, Jaller-Char JJ, Ali SK. Beyond the bull's eye:  recognizing Lyme disease. J Fam Pract. 2016;65(6):373-379.

26. Lantos PM, Charini WA, Medoff G, Moro MH, Mushatt DM, Parsonnet J, et al. Final report of the Lyme Disease Review Panel of the Infectious Disases Society of America. CID. 2010;51(1):1-5.

27. Johnson L, Stricker RB. Final report of the Lyme Disease Review Panel of the Infectious Diseases Society of America: A pyrrhic Victory? [letter] CID. 2010;51(9):1108-9.

28. Stricker RB, Johnson L. Lyme disease: the next decade. Infection Drug Resistance. 2011;4:1-9.

29. Aucott JN. Posttreatment Lyme disease syndrome. Infect Dis Clin North Am. 2015;29(2):309-323.

30. Lantos PM, Auwaerter PG, Wormser GP. A Systematic review of Borrelia burgdorferi morphologic variants does not support a role in chronic Lyme disease. CID. 2014;58(5):663-671.

31. Marques A. Chronic Lyme disease: An appraisal. Infect Dis Clin North Am. 2008;22(2):341-360.

32. Koedel U, Fingerle V, Pfister HW. Lyme neuroborreliosis - epidemiology, diagnosis and management. Nat Rev Neurol. 2015;11:446-456.

33. Shadick NA, Phillips CB, Sangha O, Logigian EL, Kaplan RF, Wright EA, et al. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med. 1999;13(12):919-926.

34. Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms.  Int J Epidiomiol. 2005;34:1340-1345.

35. Berende A, ter Hofstede HJM, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. New Eng J Med. 2016;374(13):1209-1220.

36. Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92.

37. Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, et al. Study and treatment of post Lyme disease (STOP-LD). A randomized double masked clinical trial. Neurology. 2003;60:1923-1930.

38. Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, et al. A randomized, placebo-controlled trial of repeated IV antibiotic thearpy for Lyme encephalopathy.  Neurology. 2008;70:992-1003.

39. Lyme Disease Network. [Internet]. East Brunswick (NJ): Lyme Disease Network. Burrascano JJ. Advanced Topics in Lyme Disease. Diagnostic hints and treatment guidelines for lyme and other tick borne illnesses. 2008. [cited August 4, 2016]. Available at:  http://www.lymenet.org/BurrGuide200810.pdf.

40. Lantos PM. Chronic Lyme disease. Infect Dis Clin North Am. 2015;29:325-340.

41. Lantos PM, Shapiro ED, Auwaerter PG, Baker PJ, Halperin JJ, McSweegan E et al. Unorthodox alternative therapies marketed to treat Lyme disease. CID. 2015;60(12):1776-82.

42. Hengge UR, Tannapfel A, Tyring SK, Erbel R, Arendt G, Ruzicka T. Lyme borreliosis. Lancet Infect Dis. 2003;3:489-500.

43. Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis. A review. JAMA. 2016;315(16):1767-1777.

44. Onyett, H. Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Lyme disease in Canada: Focus on children. Paediatr Child Health. 2014;19(7):379-382.