Immune modulating drug affects Lyme disease test, delays diagnosis

Welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. I find that the best way to get to know Lyme disease is through reviewing actual cases. In this episode, I will be discussing the case of a young woman with multiple sclerosis (MS), who had a delay in diagnosis of Lyme disease due to immune modulating drug effects.

Sjöwall and colleagues describe the case in an article entitled “Case Report: Borrelia-DNA Revealed the Cause of Arthritis and Dermatitis During Treatment With Rituximab,” published in Frontiers in Neurology.¹

The case involves a 20- year-old woman, who was diagnosed with multiple sclerosis (MS) at age 17. She was initially treated with tocilizumab to manage her MS.  Tocilizumab, a biological disease-modifying anti-rheumatic drug (DMARD), is used to treat rheumatoid arthritis. It’s marketed in the U.S. as Actemra.

Tocilizumab is a monoclonal antibody which blocks signals from IL-6 receptors. The drug can lower the immune system’s ability to fight infections.

The drug has received a lot of coverage in the news lately as a possible treatment for some COVID-19 patients. “Tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival,” writes Salama and colleagues in the New England Journal of Medicine.²

The most common conventional DMARDs are methotrexate, sulfasalazine, hydroxychloroquine, azathioprine, and leflunomide.

Treatment with Rituximab

Eighteen months after receiving tocilizumab, the young woman was prescribed off-label treatment with Rituximab, a medication used to treat certain types of cancer and autoimmune diseases. In the U.S., it is sold under the brand name Rituxan.

Rituximab is a monoclonal antibody directed against the B-cell lineage specific CD20. The drug, which suppresses B cell production, can weaken the immune system, making patients more susceptible to infections.

Lyme-like symptoms emerge

Three years later the young woman was evaluated for a 6-month history of arthritis in her knee and the presence of two circular erythematous rashes on her ankle.

“The right knee had typical signs of inflammation with rubor, tumor, and calor accompanied by a discretely reduced range of motion,” the authors explain.

“Our case clearly illustrates that, during treatment with B-cell depleting therapies, infections may give rise to an atypical clinical picture as well as a weak serological response to specific pathogens.”

“A dermatologist interpreted the skin symptoms as possible panniculitis with atypical erythema nodosum as a potential alternative diagnosis.”

At the onset of symptoms, Lyme disease tests were borderline. “The [test] results were interpreted to be of uncertain clinical significance,” the authors write. They add, “there were an enduring clinical suspicion of Borrelia infection.”

Biopsy confirms Lyme disease 

Clinicians diagnosed Lyme disease based on a skin biopsy of the lesions on her ankle. “Borrelia-DNA was detected in the biopsy analyzed by polymerase chain reaction (PCR),” the authors explain.

After a 3-week course of treatment with doxycycline, both the arthritis and rash resolved.

Risks of immune-modulating therapies

A number of immunomodulating treatments (IMTs) are widely used in patients with MS and other autoimmune diseases. “B-cell depleting therapies are widely used in MS as well as in many other autoimmune diseases, often with a dramatic anti-inflammatory effect and symptom relief,” write the authors.

However, there are risks associated with IMTs, particularly with B-cell depleting therapies, including an increased risk of infections, the authors wrote.

Doctors typically screen for infections prior to starting patients of IMTs to avoid immune modulating drug effects.  In this case, the girl appeared to contract Lyme disease after the start of the the Immune modulating drug effects of Rituximab.

Conclusion: “This case highlights that Borrelia-specific antibody levels cannot be reliably interpreted in patients who have received B-cell depleting therapy,” the authors write. As this case demonstrates, “an ongoing infection can easily be overlooked or misinterpreted due to a weak serological response during treatment with a B-cell depleting drug.”

The following questions are addressed in this podcast episode: 

1. Why do doctors rely on B cells to diagnose Lyme disease?
2. What are examples of B cell tests?
3. Why are B cells important in autoimmune disease?
4. How did these doctors diagnose multiple sclerosis?
5. How reliable are the tests for multiple sclerosis?
6. What are DMARD drugs?
7. What are examples of DMARDs drugs?
8. What is tocilizumab?
9. What are the risks of tocilizumab?
10. What are the benefits of tocilizumab?
11. What is rituximab?
12. What is rituximab used for?
13. How did Lyme disease present in this case?
14. Why was there a 6-month delay in treatment of the patient’s Lyme disease?

Thanks for listening to another Inside Lyme Podcast. You can read more about these cases in my show notes and on my website @DanielCameronMD.com. As always, it is your likes, comments, reviews, and shares that help spread the word about Lyme disease. Until next time on Inside Lyme.

Please remember that the advice given is general and not intended as specific advice as to any particular patient. If you require specific advice, then please seek that advice from an experienced professional.