When MS Treatment Masks Lyme Disease
Lyme disease testing can fail in patients receiving immune-modulating therapies. Some medications used to treat autoimmune diseases suppress the very immune response that Lyme disease tests rely on to detect infection.
Welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. One of the best ways to understand Lyme disease is through reviewing real clinical cases.
In this episode, I discuss a case of Lyme disease that emerged during treatment for multiple sclerosis (MS). Immune-modulating medications interfered with antibody production, delaying diagnosis and illustrating an important limitation of standard Lyme testing.
For a broader overview of diagnostic challenges, see my guide to Lyme disease test accuracy.
Immune-suppressing medications such as rituximab can prevent the body from producing antibodies. Because standard Lyme disease tests detect antibodies, these medications can lead to false-negative or borderline results even when infection is present.
Case Report of Lyme Disease During MS Treatment
Sjöwall and colleagues describe this 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.
The patient was a 20-year-old woman diagnosed with multiple sclerosis at age 17. She was initially treated with tocilizumab, a biological disease-modifying anti-rheumatic drug marketed in the United States as Actemra.
Tocilizumab blocks IL-6 receptor signaling and is commonly used for autoimmune conditions such as rheumatoid arthritis. While effective for inflammation, it can reduce the immune system’s ability to fight infections.
Treatment With Rituximab
Eighteen months later, the patient began off-label treatment with rituximab (Rituxan), a monoclonal antibody used for certain autoimmune diseases and cancers.
Rituximab targets the CD20 receptor on B-cells and depletes these antibody-producing immune cells.
This has an important implication for Lyme disease diagnosis: B-cells are responsible for producing the antibodies that Lyme disease tests detect.
When B-cells are depleted, patients may not produce measurable antibodies even when infection is present.
Lyme-Like Symptoms Appear
Three years later, the young woman developed a six-month history of knee arthritis along with two circular erythematous rashes on her ankle.
The authors describe the findings:
“The right knee had typical signs of inflammation with rubor, tumor, and calor accompanied by a discretely reduced range of motion.”
A dermatologist initially interpreted the rash as possible panniculitis with atypical erythema nodosum.
Lyme disease testing was performed but returned borderline results. The authors reported that the results were interpreted as being of uncertain clinical significance despite continued suspicion for Borrelia infection.
Because rituximab had depleted B-cells, the patient could not mount the antibody response typically detected by Lyme disease tests.
Biopsy Confirms Lyme Disease
Clinicians ultimately diagnosed Lyme disease after performing a biopsy of the skin lesions.
“Borrelia-DNA was detected in the biopsy analyzed by polymerase chain reaction (PCR),” the authors explain.
After a three-week course of doxycycline, both the arthritis and the rash resolved.
This case demonstrates that when antibody testing is unreliable due to immune suppression, direct detection methods such as PCR or tissue biopsy may be required.
Standard Lyme disease testing depends on the immune system’s ability to produce antibodies. When medications suppress B-cells, the immune system may not generate detectable antibodies, creating a diagnostic blind spot. In these cases, clinicians must rely more heavily on clinical judgment, exposure history, and alternative testing methods such as PCR or tissue biopsy.
Why Immune-Modulating Therapies Can Affect Lyme Diagnosis
B-cell depleting therapies are increasingly used to treat autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and vasculitis.
While these medications can dramatically reduce inflammation, they also increase the risk of infection.
Doctors typically screen patients for infections before starting these therapies. However, infections acquired afterward may be harder to diagnose because the immune system is suppressed.
This creates a situation where patients may have an active infection but fail to produce the antibodies that standard diagnostic tests rely upon.
Why Lyme Disease Testing May Fail
Standard Lyme disease testing relies on two-tier antibody testing:
- ELISA screening test
- Western blot confirmation
These tests detect IgM and IgG antibodies produced in response to Borrelia burgdorferi.
However, when medications suppress B-cells:
- Antibody production may be reduced
- Lyme tests may appear negative or borderline
- Active infection may still be present
The authors conclude that Borrelia-specific antibody levels cannot be reliably interpreted in patients receiving B-cell-depleting therapy.
Frequently Asked Questions
Do immune-modulating drugs affect Lyme disease test accuracy?
Yes. B-cell-depleting therapies such as rituximab suppress antibody production, which can lead to false-negative or borderline Lyme disease tests.
Which medications can affect Lyme disease testing?
Rituximab, ocrelizumab, and other CD20-targeting monoclonal antibodies may interfere with antibody production. Corticosteroids and other immunosuppressive medications may also affect testing.
How should Lyme disease be diagnosed in immunosuppressed patients?
When antibody testing is unreliable, clinicians may rely on PCR testing, tissue biopsy, clinical symptoms, and exposure history.
Can patients on immunosuppressive therapy still develop Lyme disease?
Yes. Immunosuppressive medications can increase susceptibility to infections, including Lyme disease and other tick-borne illnesses.
Related Reading
References
- Sjöwall J, Xirotagaros G, Anderson CD, Sjöwall C, Dahle C. Case Report: Borrelia-DNA Revealed the Cause of Arthritis and Dermatitis During Treatment With Rituximab. Front Neurol. 2021;12:645298.
- Salama C, Mohan SV. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. Reply. N Engl J Med. 2021;384(15):1473-1474.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Thank you Dr. Cameron for all the case studies.
The above case study makes one think, how many Lyme patients may be mistreated or not treated at all. In my case after 10 years of suffering Lyme like symptoms, the doctor just wrote a note on my file ’Definately not an Infectious Disease’. He failed to comment, what is wrong eith me.
Would you kindly describe so called ACA? I suspect the infection from childhood, with aching knees and awakening from sleep with crying spells. My parents could not calm me down.
I can send you a picture os suspected ACA, purple color skin area with tissue damage, wrinkles, including sleep disorder, pain all over, including walking difficulty among other things.
I have not found a dermatologist or dermatopathologist to help me with a acrodermatitis chronica atrophicans (ACA) rash. I have had to make clinical decisions based on other factors including sleep issues and pain.
I was diagnosed with lyme disease. My blood work was sent to mayo clinic, it came back positive. I had the quintessential bullseye rash as well. I was on doxycycline for a week but developed a rash so my PCP switched my antibiotic to amoxicillin for another 10 days. I feel better but not 100%. Can lyme disease be eradicated? I did take oil of oregano the entire time I was on antibiotics as well as florastor. I read an article that taking oil of oregano with doxycycline will eradicate lyme disease. Do you believe that to be true?
I have some Lyme disease patients who have benefited from additional antibiotic. For example, amoxicillin is not effective for several tick borne illnesses including Babesia, Bartonella, and Anaplasmosis. I have also had to look for another cause of their illness. I do not have enough information to share whether oil of oregano is effective.