Can Lyme Disease Trigger MCAS?

Lyme disease and MCAS can share symptoms
Borrelia can activate mast cells
A causal link to MCAS remains unproven

Can Lyme disease trigger mast cell activation syndrome (MCAS)? Patients often ask this after developing flushing, itching, gastrointestinal symptoms, lightheadedness, palpitations, or new reactions to foods and medications during or after Lyme disease.

There is a biologically plausible connection, but the clinical evidence remains limited. Laboratory studies show that Borrelia burgdorferi, the bacterium that causes Lyme disease, can interact with and activate mast cells.^1,2 These experiments do not establish that Lyme disease causes mast cell activation syndrome in humans.

A 2023 study adds an interesting clinical observation. Among 544 patients evaluated for MCAS, 80—or 12%—carried an ICD-10 diagnosis of unspecified Lyme disease.³ However, the study was not designed to determine whether Lyme disease causes MCAS, and the authors reported that MCAS appeared to predate the infections in many of these patients.

The distinction matters: mast-cell activation is a biological process. MCAS is a clinical syndrome requiring a much more specific evaluation.

What Is the Difference Between Mast-Cell Activation and MCAS?

Mast cells are immune cells concentrated near blood vessels, nerves, skin, and the lining of the respiratory and gastrointestinal tracts. They respond to allergens, infections, physical stimuli, medications, and other signals by releasing histamine, tryptase, prostaglandins, leukotrienes, cytokines, and other mediators.

Mast-cell activation is a normal part of immune defense. It can also occur in allergies, anaphylaxis, infections, mastocytosis, and other conditions. Mast-cell activation by itself is not the same as MCAS.

MCAS is a clinical syndrome that has received increasing attention from patients and clinicians, but important uncertainties remain regarding its mechanisms, classification, and diagnosis.^4,5

Consensus-based approaches generally look for recurrent systemic symptoms consistent with mast-cell mediator release, objective biochemical evidence of mast-cell activation during an episode, and improvement with appropriate mediator-directed treatment.^4,5

This distinction is particularly important in patients with Lyme disease because symptoms alone may overlap with several other conditions.

What Does the Lyme Disease Research Show?

A 1999 laboratory study exposed rat and mouse mast cells to live or disrupted B. burgdorferi. The investigators observed low but detectable degranulation and production and release of the inflammatory cytokine tumor necrosis factor alpha.¹

This provided experimental evidence that the Lyme spirochete can activate mast cells under laboratory conditions.

A later study examined primary mouse mast cells in the presence of B. burgdorferi and tick salivary gland extract. The investigators found evidence that mast cells participate in the local immune response during Borrelia infection and may influence transmission and dissemination in an experimental mouse model.²

These studies provide biological plausibility for mast-cell involvement in Lyme disease. They do not show how frequently clinically significant mast-cell activation occurs in patients with Lyme disease or how often those patients meet diagnostic criteria for MCAS.

What Did the Study of 544 MCAS Patients Find?

Palmer and colleagues published a study in 2023 examining chemical intolerance and mast-cell activation in 544 patients from a clinical practice specializing in MCAS.³

The primary purpose of the study was to investigate the relationship between MCAS and chemical intolerance—not Lyme disease.

Nevertheless, the researchers reviewed ICD-10 diagnoses recorded among these patients. They reported that 59% had diagnoses classified under infection. Among the entire MCAS cohort, 80 patients—or 12%—had an ICD-10 diagnosis of unspecified Lyme disease.³

Patients in the cohort also commonly had diagnoses or symptoms involving fatigue, gastrointestinal complaints, skin problems, cognitive impairment, chronic pain, orthostatic hypotension, palpitations, and dizziness.³

These findings are interesting because many of these complaints can also occur in patients evaluated for Lyme disease, autonomic dysfunction, allergy, and other multisystem illnesses.

However, the study does not show that 12% of people with Lyme disease develop MCAS. It looked in the opposite direction: researchers started with a selected group of patients evaluated for MCAS and examined the diagnoses already present in their medical records.

Did Lyme Disease Cause MCAS in These Patients?

The authors did not conclude that it did.

In fact, they specifically considered whether infections might have produced secondary MCAS and reported that the histories of many infected patients suggested their mast-cell-related illness had existed for years before the infections were identified.³

The investigators therefore proposed that infections could have acted as additional triggers or aggravating factors in some patients rather than being the original cause of their MCAS.³

There are also important limitations. The patients came from the same clinical practice, there was no control group of Lyme disease patients without MCAS, and the study was not designed to calculate the risk of MCAS following Lyme disease. The authors themselves called for independent replication of their findings.³

This makes the study useful for generating questions, but not for proving that Lyme disease causes MCAS.

Why Do Lyme Disease and MCAS Appear to Overlap?

Symptoms reported in Lyme disease, MCAS, and autonomic disorders such as POTS can resemble one another. These may include:

• Flushing, itching, hives, or swelling
• Abdominal pain, nausea, diarrhea, or food-associated symptoms
• Lightheadedness, rapid heart rate, or blood-pressure changes
• Shortness of breath, throat symptoms, or wheezing
• Headache, fatigue, and cognitive difficulties
• Temperature sensitivity
• Apparent reactions to medications, foods, odors, or environmental exposures

These symptoms are not specific to MCAS.

Dysautonomia can produce palpitations, gastrointestinal dysmotility, sweating abnormalities, temperature intolerance, and orthostatic symptoms. A 2024 review described the possible relationship between autonomic dysfunction and persistent symptoms following Lyme disease while emphasizing that research in this area remains limited.⁶

Food allergy, chronic urticaria, medication reactions, alpha-gal syndrome, hereditary alpha-tryptasemia, mastocytosis, endocrine disorders, and other illnesses may also enter the differential diagnosis.

This overlap is particularly important when evaluating chemical sensitivity in a patient with Lyme disease. Sensitivity to smells, foods, or medications does not independently establish MCAS.

Could Lyme Disease Be a Trigger or Contributing Factor?

It is reasonable to investigate whether Lyme disease may act as a trigger or contributing physiologic stressor in selected patients. Infections can activate immune pathways, and experimental studies demonstrate that B. burgdorferi can interact with mast cells.^1,2

The Palmer study also raises the possibility that infections may aggravate mast-cell-related illness in some patients, although it does not establish Lyme disease as the cause.³

Still, biologic plausibility and clinical coexistence are not the same as demonstrated causation. Published research has not established how frequently Lyme disease leads to secondary MCAS or identified a reliable pathway from Lyme infection to the clinical syndrome.

In my clinical practice, I have seen patients diagnosed with both Lyme disease and MCAS whose mast-cell-related symptoms improved as their broader illness was treated. Such observations can be meaningful when caring for an individual patient, but they cannot establish that Lyme disease caused MCAS.

Likewise, improvement during Lyme disease treatment does not prove that MCAS has been cured or that mast-cell-directed evaluation or care is no longer needed.

How Is Suspected MCAS Evaluated?

Current reviews caution against diagnosing MCAS from a collection of nonspecific symptoms alone.^4,5

Evaluation generally begins by determining whether episodes are recurrent and systemic and whether symptoms are consistent with mast-cell mediator release.

Serum tryptase can be useful when obtained soon after a significant episode and compared with an appropriate baseline measurement. Depending on the clinical circumstances, additional mast-cell mediator testing may be considered. Test selection, timing, specimen handling, and interpretation are important.^4,5

A normal baseline tryptase does not by itself exclude every mast-cell disorder. At the same time, symptoms without objective evidence of mast-cell activation do not automatically establish consensus-defined MCAS.

Clinicians may also need to consider IgE-mediated allergy, anaphylaxis, systemic mastocytosis, hereditary alpha-tryptasemia, medication effects, endocrine or gastrointestinal disorders, and autonomic dysfunction.

Patients with tick exposure and delayed reactions to mammalian meat or related products may also require evaluation for alpha-gal syndrome after a tick bite.

Does Treating Lyme Disease Treat MCAS?

There is currently no evidence that Lyme disease treatment reliably treats or cures MCAS.

Lyme disease and MCAS should not be treated as interchangeable diagnoses. If Lyme disease is present, it warrants appropriate evaluation and treatment. If MCAS or another mast-cell disorder is present, that condition may require its own evaluation and management.

Improvement in flushing, gastrointestinal symptoms, medication tolerance, lightheadedness, or other complaints during Lyme disease treatment does not establish that infection was the sole cause. Symptoms may improve for several reasons, and some patients continue to require allergy, immunology, cardiology, neurology, gastroenterology, or other specialty care.

Emergency symptoms—including difficulty breathing, throat swelling, fainting, or signs of anaphylaxis—require immediate medical attention rather than routine outpatient evaluation.

Frequently Asked Questions

Can Lyme disease cause MCAS?

It has not been established that Lyme disease causes MCAS. Laboratory studies show that Borrelia burgdorferi can activate mast cells, and clinical observations suggest Lyme disease and MCAS can coexist, but a causal relationship with the clinical syndrome remains unproven.

Can Lyme disease trigger mast cells without causing MCAS?

Yes. Mast-cell activation is part of immune biology and is not synonymous with MCAS. Experimental studies show that B. burgdorferi can activate mast cells, but this does not mean that every patient with Lyme disease develops a mast-cell disorder.

How common was Lyme disease in the 2023 MCAS study?

Among 544 patients in the MCAS cohort, 80—or 12%—had an ICD-10 diagnosis of unspecified Lyme disease. This does not mean that 12% of Lyme disease patients develop MCAS because the study began with an MCAS population rather than a Lyme disease population.

What are possible MCAS symptoms in someone with Lyme disease?

Possible mast-cell mediator symptoms include flushing, itching, hives, swelling, abdominal cramping, diarrhea, wheezing, lightheadedness, and rapid heart rate. These symptoms have many possible causes and do not confirm MCAS by themselves.

How is MCAS diagnosed?

Consensus-based approaches consider recurrent systemic episodes, objective evidence of mast-cell mediator release, and improvement with appropriate mediator-directed treatment. Testing needs to be timed and interpreted within the clinical context.

Does treating Lyme disease cure MCAS?

No evidence shows that Lyme disease treatment reliably cures MCAS. Some patients may experience improvement in overlapping symptoms, but a confirmed mast-cell disorder may require separate evaluation and management.

Clinical Takeaway

Laboratory evidence shows that Borrelia burgdorferi can activate mast cells and influence inflammatory signaling. A clinical study also found that Lyme disease diagnoses were present in a subset of patients evaluated for MCAS. Neither finding proves that Lyme disease causes MCAS in humans.

For patients with Lyme disease and recurrent multisystem reactions, mast-cell activation may be one consideration. However, symptom overlap with autonomic dysfunction, allergy, alpha-gal syndrome, medication reactions, and other conditions makes careful evaluation important.

The most accurate conclusion remains that Lyme disease may contribute to mast-cell activation in selected patients, while a causal relationship with clinical MCAS remains unproven.

Related Articles

These articles explore conditions and symptoms that can overlap with mast-cell complaints in patients with Lyme disease.

Lyme Chemical Sensitivity: Why Smells and Chemicals Trigger Symptoms

POTS Treatment Options for Lyme Disease Patients

Why Do Some People Develop Alpha-Gal Syndrome After Tick Bites?

What Is Central Sensitization? Why Pain Can Persist After Lyme Disease

This article is for educational purposes and does not constitute medical advice, diagnosis, or treatment. Patients should discuss individual symptoms and testing with a qualified healthcare professional.

References

1. Talkington, J., & Nickell, S. P. (1999). Borrelia burgdorferi spirochetes induce mast cell activation and cytokine release. Infection and Immunity, 67(3), 1107–1115. https://doi.org/10.1128/IAI.67.3.1107-1115.1999
2. Bernard, Q., Wang, Z., Di Nardo, A., & Boulanger, N. (2017). Interaction of primary mast cells with Borrelia burgdorferi (sensu stricto): Role in transmission and dissemination in C57BL/6 mice. Parasites & Vectors, 10, 313. https://doi.org/10.1186/s13071-017-2243-0
3. Palmer, R. F., Dempsey, T. T., & Afrin, L. B. (2023). Chemical intolerance and mast cell activation: A suspicious synchronicity. Journal of Xenobiotics, 13(4), 704–718. https://doi.org/10.3390/jox13040045
4. Castells, M., Giannetti, M. P., Hamilton, M. J., Novak, P., Pozdnyakova, O., Nicoloro-SantaBarbara, J., et al. (2024). Mast cell activation syndrome: Current understanding and research needs. Journal of Allergy and Clinical Immunology, 154(2), 255–263. https://doi.org/10.1016/j.jaci.2024.05.025
5. Akin, C., Gülen, T., Castells, M. C., Oude Elberink, H., & Valent, P. (2026). Diagnosis and management of patients with mast cell activation syndromes: Status 2026. Journal of Allergy and Clinical Immunology: In Practice, 14(1), 19–28. https://doi.org/10.1016/j.jaip.2025.10.046
6. Adler, B. L., Chung, T., Rowe, P. C., & Aucott, J. N. (2024). Dysautonomia following Lyme disease: A key component of post-treatment Lyme disease syndrome? Frontiers in Neurology, 15, 1344862. https://doi.org/10.3389/fneur.2024.1344862
7. Theoharides, T. C., Kempuraj, D., & Maitland, A. (2026). Mast cell activation disorders: Mechanisms, comorbidities and look-alike. Expert Review of Clinical Immunology, 22(7), 767–787. https://doi.org/10.1080/1744666X.2026.2699311

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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