Why Immune Overreaction Can Stall Recovery
People with chronic Lyme disease often feel like their body is “overreacting” to everything. Foods, supplements, exercise, weather or altitude changes, smells, medications, and even stress. Reactions that don’t make sense, treatments that once helped suddenly become intolerable, and symptoms that flare without warning.
For many Lyme patients, this pattern is driven by Mast Cell Activation Syndrome (MCAS), a condition involving immune system dysregulation that is frequently overlooked in chronic illness.
Understanding MCAS can explain why Lyme treatment stalls, why detox is so difficult, and why symptoms feel unpredictable rather than linear.
What Is Mast Cell Activation Syndrome (MCAS)?
Mast cells are immune cells found throughout the body, particularly in tissues that interface with the environment: the gut, skin, lungs, and nervous system. Their job is to detect threats and release chemical mediators, such as histamine to protect the body.
In MCAS, mast cells become hyper-reactive.
Instead of responding only to real threats, they release inflammatory mediators inappropriately, leading to widespread symptoms across multiple systems.
Unlike classic allergies, MCAS reactions:
- Are often inconsistent and can impact any part of the body
- May not show up on standard allergy testing
- Can involve dozens of triggers rather than one
Common MCAS Symptoms in Lyme Patients
MCAS symptoms overlap heavily with chronic Lyme disease, which is why it’s often missed.
Common symptoms include:
- Histamine intolerance and food sensitivities
- Flushing, itching, hives, rashes, and swelling (especially in the face)
- Brain fog, anxiety, or panic reactions
- Heart palpitations or lightheadedness
- Digestive issues (bloating, nausea, diarrhea)
- Medication or supplement intolerance
- Reacting to environmental toxins such as mold, EMFs, and VOCs.
How Is MCAS Tested and Diagnosed?
MCAS can be challenging to confirm with testing alone. Many patients with clear, classic symptoms have normal laboratory results, which is why MCAS is often considered a clinical diagnosis based on symptom patterns and response to treatment.
That said, testing can still provide helpful information and help rule out other conditions. Common labs that may be considered include:
Mast Cell Mediators
- Serum tryptase (often normal in MCAS, but helpful if elevated), Plasma histamine, Urinary N-methylhistamine, Prostaglandin D2 or 11-β-PGF2α, Chromogranin A
Inflammation and Immune Markers
- Cytokine panels, Complement markers (C3a, C4a), VEGF, MMP-9
Mold and Biotoxin Assessment
- Urine mycotoxin testing, Visual Contrast Sensitivity (VCS) testing, HLA-DR genetic susceptibility
Because mast cell mediators fluctuate, results can be normal even when symptoms are severe. For this reason, many experienced clinicians rely heavily on clinical history and symptom response to mast-cell-targeted treatments rather than labs alone.
Why MCAS and Lyme Disease Frequently Occur Together
Chronic Lyme creates the perfect environment for mast cell dysfunction.
Long-standing infections place continuous stress on the immune system, leading to:
- Persistent immune activation
- Inflammatory signaling that never fully shuts off
- Increased sensitivity to internal and external stressors
Over time, mast cells may become “stuck” in an activated state, responding as if the body is constantly under threat.
This is why many patients feel worse during treatment rather than better.
The Mold–MCAS–Lyme Connection
One of the most important (and under-recognized) drivers of MCAS in Lyme patients is mold and mycotoxin exposure.
Mycotoxins are potent immune irritants. In susceptible individuals, they can:
- Directly activate mast cells
- Increase histamine release
- Disrupt immune tolerance
- Hinder people from getting better to this environmental exposure
For patients with both Lyme and mold exposure, MCAS often becomes the “missing link” that explains:
- Extreme treatment sensitivity
- Inability to tolerate detox
- Worsening symptoms despite correct protocols
Why MCAS Can Make Lyme Treatment Feel Impossible
Many patients with undiagnosed MCAS experience:
- Severe MCAS reactions that may be confused as Herxheimer reactions
- Intolerance to antimicrobials
- Flares from detox therapies
- Regression when treatments are increased
This doesn’t mean treatment is wrong, it means the immune system is over-responding and ends up sending a warning signs signaling the body to release histamine.
MCAS, Detoxification, and Chemical Sensitivity
Mast cells play a major role in how the body tolerates detoxification.
When mast cells are activated:
- Detox pathways become reactive rather than supportive
- Patients feel worse instead of relieved
- Even gentle detox strategies can trigger flares
Focusing on stabilizing mast cells prior to treatment is key, and supporting detox must be paced and individualized, especially in MCAS-sensitive patients.
The Nervous System’s Role in MCAS
MCAS is not just an immune issue, it is also closely tied to nervous system regulation.
The autonomic nervous system communicates directly with mast cells. Chronic stress, trauma, or prolonged illness can keep the body in a survival mode, cell danger response, and perpetuate immune activation.
This explains why:
- Stress worsens symptoms
- Reactions feel sudden and disproportionate
- Patients struggle to “calm” their system even with treatment
In chronic Lyme, immune regulation and nervous system regulation must be addressed together.
Regulating the Nervous System: A Cornerstone of MCAS Recovery
MCAS is not only an immune condition, it is deeply connected to the nervous system.
Mast cells communicate directly with the autonomic nervous system. When the body is stuck in fight-or-flight, mast cells are more easily triggered and stay activated longer.
This is why nervous system regulation is not optional in MCAS recovery, it is essential.
Helpful strategies may include:
Vagus Nerve Support
- Slow diaphragmatic breathing and extended exhale breathing, Humming, gargling, or singing, Very gentle yoga or stretching
Limbic System and Brain Retraining
- Programs such as Primal Trust, DNRS (Dynamic Neural Retraining System) by Annie Hopper, Gupta Program
These programs aim to reduce chronic threat signaling in the brain that keeps the body in a state of hyper-reactivity.
Emotional Regulation Tools
- EFT tapping, Somatic therapies, Trauma-informed approaches
Many patients find that as their nervous system becomes more regulated, mast cell reactions decrease, treatment tolerance improves, and symptoms become less volatile.
MCAS as a Missing Piece — Not a Diagnosis to Fear
MCAS is not a dead end. For many patients, recognizing mast cell involvement becomes a turning point.
When MCAS is addressed:
- Treatment tolerance often improves
- Detox becomes manageable
- Reactions lessen over time
- Progress becomes steadier and more predictable
The goal is not to suppress the immune system, but to restore balance and resilience.
Why a Whole-Body Approach Matters
Chronic Lyme disease is rarely a single-issue condition. MCAS highlights why recovery requires addressing:
- Infections
- Immune regulation
- Environmental factors
- Detox capacity
- Nervous system signaling
Approaching Lyme in isolation often misses these critical layers.
Treatment Approaches for MCAS: Conventional and Functional Options
MCAS treatment is highly individualized and often requires a combination of approaches.
Conventional and Prescription-Based Options
Under medical supervision, some patients benefit from:
- H1 antihistamines (such as cetirizine or loratadine)
- H2 blockers (such as famotidine)
- Ketotifen (a mast cell stabilizer and antihistamine)
- Cromolyn sodium (targets mast cells in the gut)
- Low-dose naltrexone (LDN) to support immune modulation and inflammation control
These medications can help reduce mast cell mediator release and improve symptom stability.
Functional and Integrative Support
Many patients also benefit from natural mast cell stabilizers and immune-calming therapies, including:
- Quercetin (best tolerated when COMT genetic variants are not present)
- Luteolin
- Vitamin C
- DAO enzymes to support histamine breakdown
- Lemon balm
- Turmeric/curcumin (when tolerated)
- Antronex (supports histamine metabolism and liver function)
- Peptides such as KPV, which may help regulate inflammation and immune signaling
Dosing and tolerance can vary significantly. In MCAS patients, starting low and going slow is essential.
Diet and MCAS: Reducing Histamine Load
Diet plays a major role in mast cell activation.
For many patients, a low-histamine diet can significantly reduce daily symptom burden.
General dietary principles include:
- Avoiding fermented, aged, or cured foods
- Avoiding leftovers that sit in the refrigerator for several days
- Freezing leftovers if they will not be eaten within 24 hours
- Eating freshly prepared foods whenever possible
Histamine increases as food sits, even in the refrigerator. The longer food is stored, the higher the histamine content can become.
Examples of higher-histamine foods include:
- Tuna and other canned or processed fish, chocolate, strawberries, avocados, aged cheeses, alcohol, vinegar and fermented foods
Not every patient reacts to the same foods, which is why individualized dietary strategies are often necessary.
MCAS Is Real, Complex, and Highly Individualized
MCAS is a real and often debilitating condition, yet it remains under-recognized and under-supported in conventional healthcare.
Many patients are told:
- “Your labs are normal.”
- “It’s just anxiety.”
- “You’re too sensitive.”
But MCAS is complex, multi-systemic, and deeply influenced by:
- Infections such as Lyme
- Mold and environmental toxins
- Nervous system dysregulation
- Genetics
- Hormones
- Immune signaling
There is no single protocol that works for everyone. Treatment must be highly individualized, layered, and paced carefully.
At The Lyme Specialist, we have not only treated MCAS in our patients, we have lived through it ourselves. We understand how confusing, isolating, and frightening this condition can be, especially when standard approaches fail.
Our approach focuses on identifying root causes, stabilizing the immune system, regulating the nervous system, addressing environmental factors, and building treatment plans that patients can actually tolerate. Read the 7 root causes of Mast Cell Activation Syndrome to discover the root causes of MCAS.
Healing is possible, even when it feels out of reach.
For additional information, Dr. Bruce Hoffman
