Many people with Ehlers-Danlos Syndrome describe a frustrating pattern:
foods that were fine last week suddenly cause problems. Skin flushes for no clear reason. Headaches appear out of nowhere. You might feel nauseated, itchy, foggy, shaky or suddenly exhausted.
Often, allergy testing comes back “normal.”
And that can leave you feeling dismissed or confused.
In this article, we’ll gently explore how mast cells may be involved in some people with EDS, what we currently understand (and what we don’t), and how to approach these symptoms in a steady, grounded way.
Mast cells are part of your immune system.
They act a bit like “alarm cells.” When they detect something potentially threatening — such as infection, allergens or injury — they release chemical messengers. These messengers help your body respond.
One of those chemicals is histamine. Others include prostaglandins and cytokines.
In the right context, this process is protective. It helps fight infection and supports healing.
The difficulty arises when mast cells activate too easily or too often.
When mast cells release their chemical messengers inappropriately or excessively, symptoms can appear across multiple body systems.
This is sometimes described under the umbrella of mast cell activation syndrome (MCAS).
It’s important to note that MCAS is still an evolving area of research. Diagnostic criteria are specific, and not everyone with histamine-type symptoms meets formal criteria. However, patterns of mast cell sensitivity are increasingly recognised in complex, multisystem conditions — including EDS.
EDS affects connective tissue, which is present throughout the body — including in blood vessels, the gut lining and tissues that house immune cells.
Some researchers propose that connective tissue differences may influence how mast cells are distributed or regulated. Others suggest that chronic nervous system stress may lower the threshold for mast cell activation.
At this stage, we can say there is observed overlap between EDS, dysautonomia and mast cell activation patterns.
We cannot yet say that one directly causes the other.
What we see clinically is that some individuals experience all three patterns together.
Mast cell-related symptoms are often inconsistent.
You might react to a food one day and tolerate it the next. Heat may trigger flushing. Stress may worsen gut symptoms. Hormonal shifts can change everything.
Standard allergy tests often come back negative because mast cell activation is not always a classic IgE-mediated allergy.
This unpredictability can feel destabilising. It can also make you question yourself.
Many people are told their symptoms are anxiety-driven. While stress can absolutely amplify mast cell activation, that doesn’t mean the symptoms are imagined. The physiological response is real.
People experiencing mast cell sensitivity often report symptoms such as:
Not everyone experiences all of these. Some have mostly gut symptoms. Others primarily notice skin or neurological changes.
The autonomic nervous system and mast cells communicate with each other.
When the body is in a heightened stress state — whether due to chronic pain, trauma history, infection or dysautonomia — mast cells can become more reactive.
This doesn’t mean symptoms are psychological. It means the immune and nervous systems are deeply interconnected.
For people with EDS, where the nervous system is often already compensating for blood vessel laxity or instability, this cross-talk can become amplified.
It’s understandable to want to eliminate every possible trigger immediately. However, very restrictive approaches can sometimes increase stress and worsen the overall picture.
Instead, consider a steadier framework:
First, look for broad patterns rather than single exposures. Are symptoms worse during high-stress periods? During hormonal shifts? After poor sleep?
Second, avoid aggressive elimination diets without guidance. Removing too many foods can reduce nutritional intake and increase anxiety around eating.
Third, focus on nervous system regulation alongside any dietary or medication strategies. Gentle pacing, consistent sleep timing and stress modulation can reduce overall reactivity.
Fourth, seek medical guidance if symptoms are significant. Some people benefit from antihistamines or other mast cell–targeted treatments, but this should be individualised.
Immediate medical care is important if you experience:
These situations require emergency assessment.
Consider speaking with a clinician if:
Complex symptoms deserve thoughtful assessment, not dismissal.
If your body feels like it “overreacts,” that doesn’t mean you are fragile, dramatic or anxious. It may mean your immune and nervous systems are operating with a lower activation threshold.
The goal is not to silence your body. It’s to reduce unnecessary activation and build steadier foundations underneath it.
With careful, individualised support, many people find their system becomes more predictable over time. You deserve to understand what’s happening in your body — even when the science is still catching up.
