Can Lyme disease trigger an autoimmune disease?

Adult-onset Still’s disease (AOSD) is often thought to be an autoimmune disease, but is, in fact, a systemic auto-inflammatory condition, believed to be caused by an over-reactive immune response to an infection, such as Lyme disease. As Cimmino points out, both diseases share several clinical characteristics.¹

Still’s disease can cause “a triad of high fever, salmon-colored nodular

Can Lyme Disease Trigger an Autoimmune Disease?

The relationship between Lyme disease and autoimmune disease has been debated for years. Some researchers believe infections like Lyme disease may trigger immune responses that resemble autoimmune conditions in certain patients.

Lyme disease is caused by the bacterium Borrelia burgdorferi, transmitted through tick bites. While many patients recover with treatment, others continue to experience persistent symptoms such as joint pain, fatigue, or neurologic complaints. These symptoms sometimes raise questions about whether Lyme disease may trigger an autoimmune process.

Can infection trigger autoimmune disease?

Infections have long been suspected as possible triggers for autoimmune disease. Researchers have studied several mechanisms by which infections might activate the immune system in ways that resemble autoimmune conditions.

One proposed mechanism is molecular mimicry. This occurs when the immune system reacts to bacterial proteins that resemble human tissue. As a result, immune responses directed against an infection may also affect the body’s own cells.

Other mechanisms that may contribute include:

• Persistent immune activation
• Inflammation following infection
• Genetic susceptibility to autoimmune reactions

Lyme disease and autoimmune arthritis

One of the most studied examples of Lyme disease and autoimmunity involves Lyme arthritis. Most patients improve with antibiotic therapy. However, a small number develop antibiotic-refractory Lyme arthritis, where joint inflammation persists even after treatment.

Some researchers have proposed that immune responses triggered by infection may continue even after the bacteria are no longer detectable.

However, this topic remains controversial, and many experts believe persistent symptoms may also reflect ongoing infection or immune dysregulation rather than classic autoimmune disease.

Symptoms that may overlap with autoimmune disease

Patients with Lyme disease may develop symptoms that resemble autoimmune conditions. These may include:

• Joint pain and swelling
• Fatigue
• Neurologic symptoms
• Muscle aches
• Cognitive difficulties

Because of this overlap, Lyme disease can sometimes be mistaken for autoimmune disorders such as rheumatoid arthritis or lupus.

Why diagnosis can be difficult

Distinguishing between Lyme disease and autoimmune disease can be challenging. Patients may have overlapping symptoms, and laboratory testing does not always provide clear answers.

Some individuals may develop autoimmune markers during infection, while others may have Lyme disease that is initially misdiagnosed as an autoimmune condition.

Understanding the role of infection is important when evaluating patients with unexplained inflammatory or neurologic symptoms.

Clinical perspective

In clinical practice, it is important to evaluate patients carefully for possible infections when symptoms resemble autoimmune disease.

Tick-borne infections such as Lyme disease and other coinfections may produce symptoms that mimic autoimmune disorders. Identifying the underlying cause can help guide appropriate treatment.

Key Point

Lyme disease may trigger immune responses that resemble autoimmune disease in some patients, but the relationship remains complex and continues to be studied.

Clinical Insight

Symptoms of Lyme disease can overlap with autoimmune disorders such as rheumatoid arthritis and lupus. Clinicians evaluating unexplained inflammatory symptoms should consider possible tick-borne infections.

Learn more in the Lyme disease hub and the tick-borne coinfections hub.

rash and arthritis and/or arthralgia,” explains Ocon in the British Medical Journal.² Lyme disease can also present with fevers, atypical rashes and arthritis and/or arthralgias.

Both conditions were first identified in children. Still’s disease was initially considered a severe version of juvenile idiopathic arthritis (JIA), while Lyme disease symptoms were originally attributed to juvenile rheumatoid arthritis (JRA).

Lyme disease and autoimmune diseases

A growing number of studies indicate that Lyme disease may trigger an autoimmune response in some individuals or symptoms may mimic an autoimmune disease.

Cross et al. describe the case of a Lyme disease patient with persistent neuropsychiatric symptoms who developed an autoimmune disorder, known as Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).³ The patient recovered following treatment with intravenous immunoglobulin (IVIG).

Investigators report the case of an elderly woman whose Lyme disease symptoms mimicked dermatomyositis (DM), a serious autoimmune disease which typically requires immunosuppressive therapy. The patient was eventually diagnosed with Lyme disease and recovered completely with antibiotic treatment.

The authors suggest, “[Lyme disease] could be a great mimicker of other autoimmune diseases like DM.”

Case Presentation: Still’s disease

A 61-year-old man presented with a “complaint of intermittent spiking fevers, night sweats, generalised malaise, as well as a history of erythematous circular rashes on his right upper extremity,” writes Ocon.²

He was diagnosed clinically with Lyme disease and received two 10-day courses of doxycycline, but continued to suffer from fevers, chest pressure, a dry cough, along with malaise and arthralgia.

The man was subsequently diagnosed with Still’s disease, as he met the criteria with a fever greater than 102.2°F for at least 1 week; a characteristic rash; a white cell count of at least 10,000; lymphadenopathy, and elevated liver transaminases.

He was treated successfully with intravenous steroids and anakinra (a humanised interleukin-1 receptor antagonist), which is used to modulate the immune system.

Author’s Takeaway:

“For the first time, we describe a case of AOSD precipitated by Lyme disease.”

“Lyme disease is a rare trigger of adult-onset Still’s disease, likely mediated via immune system inflammatory activation.”

“AOSD presented with a rare manifestation of haemorrhagic pericarditis and tamponade.”

“We believe that the immunological response to Lyme disease may have triggered AOSD via a hyper-activated immune system.”

UPDATED: July 1, 2021