This week in Morning Report, we discussed the case of a young patient requesting testing for Lyme disease due to chronic symptoms of fatigue, whole-body pain, headaches, and arthralgias. The patient had undergone a number of investigations to rule out infectious, inflammatory, autoimmune, endocrine, and neoplastic causes that might explain these symptoms, all of which were reassuringly negative.

This left us with a few increasingly common clinical practice questions: Who do we test for Lyme disease? Who is at risk? What does the testing process involve? What symptoms can be attributed to Lyme disease? And how should clinicians address ‘Chronic Lyme Disease’, which is a highly debated area lacking clear-cut evidence?

Let’s recap our interesting discussions on Lyme Disease!

1. What is Lyme disease, who gets it, and how?

As always, let’s start off by going back to basics and understanding the history, epidemiology, and pathology of this disease. Lyme Disease was initially discovered in the 1970s in Lyme, Connecticut (Medical Jeopardy question alert!) when researchers identified adults and children presenting with fatigue, swollen knees, rashes, and headaches. This was initially felt to be Juvenile Idiopathic Arthritis…until the 1980s, when Dr. Willy Burgdorfer identified a spirochete that was carrying Lyme — this was named Borrelia burgdorferi in his honour.

I’ve summarized our discussion on the ‘who’ and ‘how’ of Lyme disease in the table below:

Remember that nymph-stage ticks pose the highest risk of transmission!

2. What are the key manifestations of Lyme Disease to know about?

We discussed that Lyme disease manifests in 3 stages, described below. Estimates vary, but generally up to a quarter of patients do not recall ever having a tick bite and may not progress through each of these stages linearly.

I’ve summarized our discussion of the stages of Lyme Disease below:

Let’s take a quick side look at how heterogeneously erythema migrans can present – it doesn’t always look like the classic ‘bullseye’ rash!

In addition, it is important to remember that erythema migrans looks different on different skin tones. Also from NEJM:

3. Diagnosis of Lyme Disease

The key with Lyme is to know who should and should not be tested. In general, test only when it will change your management, and always remember the risk of false-positive results in situations where your pre-test probability of Lyme is low.

• Only suspect Lyme in patients who have a risk of exposure to Lyme-carrying ticks and clinical manifestations of Lyme disease
• Do not test asymptomatic patients as a form of ‘screening’ in endemic areas
• Do not test patients whose sole presenting symptoms are nonspecific (e.g., fatigue)

Understand the following serological tests:

• ELISA: Whole-cell based antigen. IgM, IgG, combined IgM+IgG
• Western Blot: Antibody to individual component of organism
• PCR: Not readily available or routinely done
• Culture: From skin, CSF, blood – not readily available or routinely done

And finally, remember the following testing pearls:

• Lyme testing is not reliable immediately after tick exposure – it can take several weeks for antibodies to develop. The diagnosis of early localized Lyme disease should be made on the basis of clinical suspicion alone – confirmatory serology is not needed to treat!
• Know that there may be some degree of cross-reactivity with other spirochetes that may lead to false positives (e.g., syphilis, leptospirosis)
• Know where the specimen was processed, and the test characteristics. In Ontario, Lyme testing is done using a standard recommended two-tier testing approach. There are many private ‘Lyme labs’ (especially in the United States) with higher reported rates of test positivity and unclear benchmarking/validation standards, so interpret results accordingly.

4. Quick principles of Lyme treatment

• Again, remember: if there is an erythema migrans rash, you don’t need to wait for serology – just treat!
• CNS and CV manifestations will often require parenteral antibiotics. For po antibiotics, the mainstay of treatment is doxycycline (alternatively, amoxicillin or cefuroxime), with specific regimens summarized here.
• Check out this Health Quality Ontario Clinical Guidance document which summarizes a nice approach to whether or not post-exposure prophylaxis (one-time dose of doxy) is warranted.
• In the right context, consider co-infections that often travel with Lyme. This is summarized in a great table from an excellent NEJM review on Lyme disease, below:

5. Understand more about ‘Chronic Lyme Disease’

As you will likely encounter, there is a large amount of information and misinformation about Lyme Disease in the public sphere. It is very important to distinguish between Post-Treatment Lyme Disease Syndrome (where patients have residual symptoms after being treated for confirmed Lyme Disease) vs. Chronic Lyme Disease (which is poorly characterized, lacks a rigorous evidence base, and is often the basis for unproven treatments).

This NEJM Article entitled ‘A Critical Appraisal of Chronic Lyme Disease’ is a useful resource in understanding how to approach this entity, and this short CMAJ news piece discusses some myths surrounding the ‘Chronic Lyme industry’.

I hope you found this Morning Report useful!