Is Lyme Disease an Autoimmune Disease? What Patients Should Know

Is Lyme disease an autoimmune disease? It is one of the most common questions patients ask after being diagnosed with Lyme disease or when persistent symptoms continue despite treatment.

Lyme disease is caused by infection with Borrelia burgdorferi and is not classified as a classic autoimmune disease.

However, the relationship between Lyme disease and the immune system is complex. In some patients, Lyme disease may trigger inflammation, immune dysregulation, or symptoms that resemble autoimmune disease. Researchers continue to investigate why some individuals recover completely while others experience prolonged inflammatory symptoms after infection.

This overlap can create diagnostic confusion, especially when symptoms resemble lupus, rheumatoid arthritis, dermatomyositis, Sjögren’s syndrome, multiple sclerosis, or adult-onset Still’s disease.

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Is Lyme Disease an Autoimmune Disease?

Lyme disease begins as a bacterial infection transmitted through the bite of an infected Ixodes tick.

Autoimmune diseases develop when the immune system mistakenly attacks the body’s own tissues. Lyme disease differs because it begins with an infectious trigger rather than an abnormal immune response.

Even so, infections can activate the immune system. In some patients, that activation may persist beyond the acute infection or resemble autoimmune disease.

For this reason, many physicians distinguish between:

• Active Lyme disease infection
• Post-infectious inflammation
• Immune dysregulation following infection
• A true autoimmune disease occurring independently or alongside Lyme disease

The most accurate answer is:

Lyme disease is an infection that may trigger immune activation or autoimmune-like symptoms in selected patients, but it is not itself considered an autoimmune disease.

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Can Lyme Disease Trigger Autoimmune Disease or Autoimmune-Like Symptoms?

Whether Lyme disease can trigger autoimmune disease remains an active area of investigation.

Researchers have proposed several possible mechanisms, including molecular mimicry, persistent immune activation, bystander activation, altered cytokine signaling, and genetic susceptibility. These mechanisms may contribute to prolonged inflammation or immune dysregulation after infection.

Several reports describe patients whose Lyme disease symptoms overlap with autoimmune or inflammatory conditions.

These symptoms may include:

• Joint pain and swelling
• Muscle pain
• Fatigue
• Fever or night sweats
• Skin rashes
• Neurologic symptoms
• Cognitive dysfunction
• Elevated inflammatory markers

In some patients, Lyme disease may initially be mistaken for an autoimmune disease. In others, infection may act as an inflammatory trigger in someone already predisposed to immune dysregulation.

The challenge for clinicians is determining whether symptoms are primarily related to active infection, post-infectious inflammation, immune dysregulation, autoimmune disease, or another medical condition altogether.

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Lyme Disease Can Mimic Autoimmune Disorders

Lyme disease has long been called one of medicine’s “great imitators” because it can resemble many inflammatory and autoimmune conditions.

Patients may undergo evaluation for lupus, rheumatoid arthritis, vasculitis, dermatomyositis, Sjögren’s syndrome, inflammatory neuropathies, or multiple sclerosis before Lyme disease is recognized.

For example, Lyme arthritis may resemble inflammatory arthritis. Neurologic Lyme disease may mimic immune-mediated neurologic disorders. Muscle pain, weakness, fatigue, and atypical skin rashes may also raise concern for rheumatologic disease.

This does not mean that every autoimmune diagnosis is actually Lyme disease. Rather, Lyme disease should remain part of the differential diagnosis when compatible symptoms occur in patients with possible tick exposure.

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Lyme Disease, Lupus, and Overlapping Symptoms

Patients frequently search for information comparing Lyme disease and lupus because both illnesses can produce fatigue, joint pain, rashes, neurologic symptoms, and systemic complaints.

Lyme disease does not simply “turn into lupus.” However, both diseases can produce overlapping clinical findings, making careful evaluation essential.

The goal is not to replace one diagnosis with another, but to avoid overlooking an infectious illness when the history suggests tick exposure or Lyme disease risk.

Likewise, clinicians should avoid attributing every persistent inflammatory symptom to Lyme disease when an autoimmune disorder may also be present.

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Can Lyme Disease Trigger Adult-Onset Still’s Disease?

Adult-onset Still’s disease (AOSD) is now generally considered a systemic autoinflammatory disorder rather than a classic autoimmune disease.

AOSD is characterized by high fever, rash, arthritis, elevated inflammatory markers, and systemic inflammation. Lyme disease can also present with fever, atypical rashes, arthritis, and arthralgias, creating significant diagnostic overlap.

More than three decades ago, Cimmino and Trevisan described Lyme arthritis presenting as adult-onset Still’s disease. More recently, Ocon and colleagues reported a patient whose adult-onset Still’s disease developed after acute Lyme disease, raising the possibility that infection triggered an exaggerated inflammatory response.

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Case Report: Adult-Onset Still’s Disease Following Lyme Disease

Ocon and colleagues described a 61-year-old man who initially presented with intermittent spiking fevers, night sweats, malaise, arthralgia, and erythematous circular rashes involving his right upper extremity.

He was diagnosed clinically with Lyme disease and treated with two 10-day courses of doxycycline.

Despite treatment, he continued experiencing persistent fever, chest pressure, dry cough, fatigue, and worsening inflammatory symptoms.

Subsequent evaluation demonstrated that he met diagnostic criteria for adult-onset Still’s disease, including prolonged fever, characteristic rash, leukocytosis, lymphadenopathy, and elevated liver enzymes.

He improved after treatment with corticosteroids and anakinra, an interleukin-1 receptor antagonist used to treat adult-onset Still’s disease.

The authors proposed that Lyme disease may have triggered adult-onset Still’s disease through immune system inflammatory activation.

Because this was a single case report, it cannot establish that Lyme disease causes adult-onset Still’s disease. However, it illustrates how infection may occasionally precede dysregulated immune activation in susceptible individuals.

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Immune Dysregulation Following Lyme Disease

Researchers continue to investigate why some patients experience prolonged inflammatory symptoms after Lyme disease.

Current theories include persistent immune activation, altered cytokine responses, residual bacterial antigens, molecular mimicry, and host genetic susceptibility.

A recent review by Wong and colleagues concluded that immune dysregulation remains one biologically plausible explanation for persistent symptoms following Lyme disease, while emphasizing that many important questions remain unanswered.

Importantly, immune dysregulation is not the same as autoimmune disease. Many patients experience prolonged inflammatory symptoms without developing a defined autoimmune disorder.

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Lyme Disease and PANS/PANDAS-Like Presentations

Cross and colleagues described a patient with persistent Lyme disease-associated neuropsychiatric symptoms who later met criteria for Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).

Following treatment that included intravenous immunoglobulin (IVIG), the patient experienced substantial clinical improvement.

Although individual case reports cannot establish causation, they illustrate how infections may interact with immune regulation in susceptible individuals and highlight the need for further research.

Learn more about PANS/PANDAS and Lyme disease.

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Clinical Perspective

Lyme disease occupies an important intersection between infectious disease, immunology, and rheumatology.

In clinical practice, Lyme disease may mimic autoimmune disease, coexist with autoimmune disease, or possibly contribute to immune dysregulation following infection.

Distinguishing among these possibilities requires careful history-taking, physical examination, laboratory evaluation, and thoughtful clinical judgment.

Patients whose symptoms fit neatly into a single diagnostic category are often easier to diagnose. However, many individuals present with overlapping infectious, inflammatory, and immune-mediated features. Lyme disease should remain part of the differential diagnosis when patients develop unexplained fever, rash, arthritis, neurologic symptoms, or inflammatory syndromes following possible tick exposure.

At the same time, not every patient with persistent symptoms after Lyme disease has developed an autoimmune disease. Some may have post-infectious immune dysregulation, while others may have an unrelated rheumatologic disorder that requires separate evaluation. Careful clinical assessment remains essential.

For patients with persistent inflammatory symptoms, the most important question is not simply whether Lyme disease is “autoimmune.” Instead, clinicians should consider whether symptoms are due to active infection, post-infectious inflammation, immune dysregulation, a primary autoimmune disease, or more than one condition occurring together.

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Frequently Asked Questions

Is Lyme disease an autoimmune disease?

No. Lyme disease is an infectious disease caused by Borrelia burgdorferi. It is not classified as a classic autoimmune disease. However, Lyme disease may trigger immune activation or autoimmune-like symptoms in some patients.

Can Lyme disease trigger autoimmune disease?

Possibly. Case reports and laboratory studies suggest that Lyme disease may trigger autoimmune or autoinflammatory responses in susceptible individuals. However, stronger clinical evidence is still needed to determine how often this occurs.

Can Lyme disease mimic lupus?

Yes. Lyme disease and lupus can both cause fatigue, joint pain, skin rashes, neurologic symptoms, and other systemic complaints. Careful clinical evaluation helps distinguish between these conditions.

Why does Lyme disease resemble autoimmune disorders?

Both Lyme disease and autoimmune diseases can produce inflammation involving the joints, nervous system, skin, heart, and other organs. These overlapping features can make diagnosis challenging.

What is adult-onset Still’s disease?

Adult-onset Still’s disease is a rare systemic autoinflammatory disorder characterized by high fevers, rash, arthritis, and elevated inflammatory markers. Infections have long been suspected of acting as triggers in some patients.

Should Lyme disease be considered before starting immunosuppressive therapy?

Yes. In patients with compatible symptoms and possible tick exposure, clinicians should consider Lyme disease and other infections before initiating long-term immunosuppressive treatment whenever clinically appropriate.

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Clinical Takeaway

Lyme disease is not a classic autoimmune disease, but it can mimic autoimmune disorders and may contribute to immune dysregulation in susceptible individuals.

Although rare case reports suggest Lyme disease may precede conditions such as adult-onset Still’s disease, current evidence supports an association rather than proving cause and effect.

Maintaining a broad differential diagnosis helps clinicians recognize both Lyme disease and autoimmune disorders while avoiding unnecessary delays in diagnosis and treatment.

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Related Articles

Lyme disease frequently overlaps with inflammatory and autoimmune conditions. These related articles explore additional clinical presentations.

• Lyme Disease Mimics an Autoimmune Disorder
• Lyme Disease and Sjögren Syndrome
• PANS/PANDAS and Lyme Disease
• Could Lyme Disease Be Associated with Guillain-Barré Syndrome?

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References

1. Cimmino MA, Trevisan G. Lyme arthritis presenting as adult-onset Still’s disease. Clin Exp Rheumatol. 1989;7(3):305-308.
2. Ocon AJ, Kwiatkowski AV, Peredo-Wende R, Blinkhorn R. Adult-onset Still’s disease with haemorrhagic pericarditis and tamponade preceded by acute Lyme disease. BMJ Case Rep. 2018;2018:bcr2018225517. doi:10.1136/bcr-2018-225517.
3. Cross A, Bouboulis D, Shimasaki C, Jones CR. Case Report: PANDAS and Persistent Lyme Disease With Neuropsychiatric Symptoms: Treatment, Resolution, and Recovery. Front Psychiatry. 2021;12:505941.
4. Wong KH, Shapiro ED, Soffer GK. A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist. Clin Rev Allergy Immunol. 2022;62(1):264-271.

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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