Lyme Disease vs Rheumatoid Arthritis: How to Tell the Difference

Is it Lyme disease or rheumatoid arthritis? Both conditions can cause joint pain, stiffness, and reduced mobility—making them easy to confuse.

Quick answer: Lyme disease can mimic rheumatoid arthritis, but the underlying cause is infection rather than autoimmune inflammation. In some cases, both conditions may coexist, complicating diagnosis and treatment.

Understanding the difference is important—because the treatment approach is very different.

Why Lyme Disease Is Mistaken for Rheumatoid Arthritis

Lyme disease can present with joint symptoms that closely resemble rheumatoid arthritis, including:

• Joint pain and swelling
• Morning stiffness
• Reduced mobility
• Fatigue

Because of this overlap, some patients are initially diagnosed with rheumatoid arthritis when Lyme disease is the underlying cause.

For a broader overview, see Lyme arthritis.

Key Differences Between Lyme Disease and Rheumatoid Arthritis

• Lyme disease: Caused by infection with Borrelia burgdorferi
• Rheumatoid arthritis: An autoimmune condition

Lyme arthritis may affect one or a few joints at a time, while rheumatoid arthritis more commonly presents with symmetrical joint involvement.

Symptoms that fluctuate or move between joints may raise suspicion for Lyme disease.

Learn more about why Lyme symptoms come and go.

When Both Conditions Occur Together

In some cases, Lyme disease and rheumatoid arthritis may coexist.

A study by Yuskevych and colleagues found that nearly 50% of patients with rheumatoid arthritis also tested positive for Lyme disease.

Patients with both conditions experienced:

• More severe joint pain
• Reduced physical activity
• Greater functional impairment
• Worse quality of life

Infection with Borrelia burgdorferi appeared to worsen both physical and psychological burden.

Mental Health and Functional Impact

Patients with overlapping Lyme disease and rheumatoid arthritis may experience a greater psychological burden.

Lower mental health scores have been observed in patients with Lyme arthritis, suggesting more difficulty adapting to chronic symptoms.

Depression and fatigue may further reduce quality of life and functional capacity.

Why Diagnosis Is Often Delayed

Lyme disease is frequently overlooked when symptoms resemble autoimmune conditions.

When joint symptoms do not respond as expected to standard rheumatoid arthritis treatments, it may be important to consider alternative explanations.

This pattern contributes to delayed Lyme disease diagnosis, where symptoms are evaluated within the wrong framework.

Key insight: Symptoms that don’t follow a typical autoimmune pattern may point toward infection rather than autoimmune disease.

Clinical Perspective

I often see patients whose symptoms were initially attributed to rheumatoid arthritis but later found to involve Lyme disease.

In some cases, what appears to be an autoimmune flare may instead reflect underlying infection or co-infection.

Recognizing this distinction can change both diagnosis and treatment strategy.

Key Takeaway

Lyme disease can mimic rheumatoid arthritis—and in some cases, both conditions may coexist.

When joint symptoms are persistent, atypical, or unresponsive to treatment, Lyme disease should be considered—especially in endemic areas.

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