Lyme Disease or Rheumatoid Arthritis? How to Tell the Difference

Quick Answer: Lyme disease can mimic rheumatoid arthritis, causing joint pain, stiffness, and fatigue—but Lyme is driven by infection, not autoimmune inflammation.

Clinical Insight: When joint symptoms don’t follow a typical autoimmune pattern—or don’t respond to treatment—it may be important to consider Lyme disease.

Joint pain. Morning stiffness. Fatigue.

Is it rheumatoid arthritis—or could it be Lyme disease?

These two conditions can look very similar, but the underlying cause—and treatment—are 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.

See our overview of 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 often affects 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 may worsen both physical and psychological burden.

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 contributes to delayed Lyme disease diagnosis.

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

How to Approach Persistent Joint Symptoms

When joint pain is persistent or unexplained, clinicians may consider:

• Exposure risk to ticks
• Fluctuating or migratory symptoms
• Lack of response to standard autoimmune therapy

See the broader Lyme disease symptoms guide.

Clinical Perspective

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

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