When Are DMARDs Used for Lyme Arthritis?
Lyme arthritis treatment decisions
DMARDs, antibiotics, and persistent joint inflammation
Why the diagnosis matters
Most patients with Lyme arthritis improve after appropriate antibiotic treatment. However, some continue to have persistent joint inflammation despite recommended therapy. In these patients, physicians face an important question: should persistent arthritis be managed with additional antibiotics, disease-modifying antirheumatic drugs (DMARDs), or another approach?
This question remains controversial because persistent joint inflammation may reflect an ongoing infection, a post-infectious immune response, an unrecognized tick-borne coinfection, or another inflammatory arthritis such as rheumatoid arthritis. Choosing the wrong treatment could expose patients to unnecessary risks.
What are DMARDs?
Disease-modifying antirheumatic drugs (DMARDs) are medications intended to slow the progression of inflammatory arthritis. Synthetic DMARDs include methotrexate, hydroxychloroquine, and sulfasalazine. Biologic DMARDs include tumor necrosis factor alpha (TNF-α) inhibitors such as infliximab (Remicade®), interleukin-1 blockers such as anakinra (Kineret®), monoclonal antibodies against B cells such as rituximab, and the T-cell costimulation blocker abatacept (ORENCIA®).
The question addressed here is not whether DMARDs have an important role in rheumatology. Rather, the question is when DMARDs are appropriate for Lyme arthritis, particularly when persistent infection has not been confidently excluded.
Why is treating Lyme arthritis sometimes difficult?
Most patients recover after recommended antibiotic treatment. However, a minority continue to have persistent synovitis, most commonly affecting one or a few large joints such as the knee. Physicians must then determine whether persistent arthritis reflects ongoing Borrelia burgdorferi infection, a post-infectious immune response, an unrecognized tick-borne coinfection, or another inflammatory arthritis such as rheumatoid arthritis. Because treatment differs for each possibility, careful evaluation is essential before starting immunosuppressive therapy.
When are DMARDs used for Lyme arthritis?
I agree with the clinical conundrum raised by Dr. Allen Steere in the Journal of Rheumatology:
- “Do [Lyme arthritis] patients with little or no apparent response to oral antibiotic therapy still have active B. burgdorferi infection requiring IV antibiotic therapy…
- do they have post-infectious [Lyme arthritis] requiring therapy with disease-modifying antirheumatic drugs…
- or do they have another form of chronic inflammatory arthritis?”1
Steere also notes that the wrong treatment could have detrimental effects. “Either IV antibiotics or DMARD, given inappropriately, might be harmful.”1
I do not agree, however, with Dr. Steere’s conclusion that “It is now clear that this complication is not caused by antibiotic resistance or failure of spirochetal killing.”1
Nor do I fully agree with his treatment approach: “We treat these patients with DMARD such as hydroxychloroquine, methotrexate, or tumor necrosis factor inhibitors, the standard of care for other forms of chronic inflammatory arthritis.”1
[bctt tweet=”The evidence supporting routine use of disease-modifying antirheumatic drugs (DMARDs) for Lyme arthritis remains limited.” username=”DrDanielCameron”]
Why is DMARD treatment controversial?
Both treatment approaches have potential drawbacks.
Additional antibiotics may lead to adverse events, including Clostridioides difficile infection, medication intolerance, or unnecessary antibiotic exposure if active infection is no longer present.
Conversely, DMARDs have their own risks and may delay appropriate antimicrobial treatment if persistent infection or an unrecognized tick-borne coinfection remains present.1
The evidence supporting the routine use of DMARDs for Lyme arthritis remains limited and is based primarily on observational studies and case series rather than randomized clinical trials.
Some experts use the term antibiotic-refractory Lyme arthritis to describe persistent synovitis after recommended antibiotic therapy, although the underlying mechanism remains debated.
In my clinical practice, I have cared for patients initially believed to have antibiotic-refractory Lyme arthritis who subsequently improved after additional evaluation and treatment for Lyme disease or a previously unrecognized tick-borne coinfection. Although these clinical observations do not establish the cause of persistent arthritis in every patient, they reinforce the importance of an individualized evaluation before initiating immunosuppressive therapy with DMARDs.
Can Lyme disease mimic rheumatoid arthritis?
Researchers at Massachusetts General Hospital described a series of 30 patients who developed systemic autoimmune joint disease following Lyme disease.
Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthropathy (SpA).2 The investigators reported that DMARD therapy reduced joint pain in these patients.
However, the study was not designed to determine whether DMARD therapy improved other Lyme disease manifestations such as fatigue, Lyme neuropathy, neuropsychiatric Lyme disease, or Lyme encephalopathy.
This distinction is important for patients trying to understand whether they have an autoimmune disease triggered by Lyme disease or whether persistent symptoms may reflect persistent infection versus an inflammatory immune response.
Can Lyme arthritis be cured?
Many patients recover completely after appropriate antibiotic treatment. Others continue to have persistent joint inflammation. In these individuals, the challenge is determining whether symptoms represent persistent infection, a post-infectious immune response, a tick-borne coinfection, or another inflammatory arthritis.
The 2020 clinical practice guidelines from the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) provide recommendations for treating Lyme arthritis after standard antibiotic therapy.3 Nevertheless, clinical judgment remains essential when patients have persistent symptoms, atypical presentations, or evidence suggesting possible coinfections.
What role does methotrexate play in Lyme arthritis?
Methotrexate and hydroxychloroquine are among the DMARDs considered by some rheumatologists when persistent arthritis is believed to reflect a post-infectious immune response or another inflammatory arthritis.
Before prescribing methotrexate or another DMARD, physicians should carefully evaluate whether persistent Lyme disease or a tick-borne coinfection has been adequately excluded, particularly when patients continue to have systemic symptoms beyond isolated joint inflammation.
Frequently Asked Questions
What are DMARDs?
DMARDs are disease-modifying antirheumatic drugs used to treat inflammatory arthritis. Examples include methotrexate, hydroxychloroquine, sulfasalazine, TNF inhibitors, rituximab, and abatacept.
When are DMARDs used for Lyme arthritis?
Some physicians consider DMARDs when persistent arthritis is believed to represent a post-infectious immune response or another inflammatory arthritis rather than ongoing infection. The decision should be individualized after careful evaluation.
Can Lyme disease mimic rheumatoid arthritis?
Yes. Lyme disease can resemble rheumatoid arthritis because both conditions may cause joint pain and swelling. Distinguishing between them is important because treatment differs.
Is methotrexate used for Lyme arthritis?
Methotrexate is sometimes considered when persistent arthritis appears immune-mediated. However, physicians should carefully evaluate for persistent Lyme disease or tick-borne coinfections before beginning immunosuppressive therapy.
Can Lyme arthritis be cured?
Many patients recover completely after antibiotic treatment. Others require further evaluation to determine whether persistent symptoms are due to ongoing infection, post-infectious inflammation, coinfection, or another inflammatory arthritis.
Clinical Takeaway
Treating persistent Lyme arthritis remains one of the more challenging decisions in clinical practice. Determining whether ongoing joint inflammation reflects persistent infection, a post-infectious immune response, an unrecognized tick-borne coinfection, or another inflammatory arthritis is critical because treatment strategies differ.
Patients should discuss the potential benefits and risks of additional antibiotics, DMARD therapy, and further diagnostic evaluation with their physician before beginning immunosuppressive treatment.
In my practice, an individualized evaluation remains essential before concluding that persistent Lyme arthritis is truly antibiotic-refractory.
Related Articles
Learn more about persistent Lyme disease, immune-mediated inflammation, and autoimmune conditions following Lyme disease.
How can doctors determine if patients with systemic autoimmune joint disease following Lyme disease don’t have persistent infection?
Can Lyme disease trigger an autoimmune disease?
Persistent Lyme infection or inflammatory immune response?
Persistent Lyme disease mechanisms
Chronic Lyme disease pain
References
- Steere AC. Treatment of Lyme Arthritis. J Rheumatol. 2019;46(8):871-873.
- Arvikar SL, Crowley JT, Sulka KB, Steere AC. Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease. Arthritis Rheumatol. 2017;69(1):194-202.
- Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clin Infect Dis. 2021;72(1):e1-e48.
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
