If you have POTS and mast cell activation syndrome (MCAS), you've probably been told they're "comorbidities" — two separate conditions that happen to coexist. But the connection between them is more direct than most people realize.
Sympathetic Pathways Aren't All the Same
One of the most important things to understand about the sympathetic nervous system is that it's not a single system. It has functionally distinct pathways — and mast cells interact with specific ones.
“We've got sympathetic, we got skin sympathetic nerve activity and then we have muscle sympathetic nerve activity and they're different, which is wild but it's different... If I'm having a histamine response it's just blasting out of control... One of the places it's gonna be active is in the skin... as it does that and we push that when we push that into the skin, we can actually have an increase in nitric oxide release or the histamine basically causes localized vasodilation in the skin.”
Skin sympathetic nerve activity and muscle sympathetic nerve activity are different systems. When histamine floods the skin pathway, it causes vasodilation in the skin — blood pools at the surface. Meanwhile, the muscle sympathetic pathway may be doing something completely different.
The Blood Flow Cascade
This matters for POTS because when blood vasodilates in the skin, it has to come from somewhere. If blood is pooling in the skin due to histamine-driven vasodilation, there's less available for the brain. The heart rate goes up to compensate.
This is why many MCAS patients notice their POTS symptoms flare during histamine reactions. It's not two separate problems happening at the same time. The histamine response is directly affecting blood distribution, which triggers the autonomic compensation.
Why the Brain Ramps Up
When the brain detects that blood flow isn't adequate, it doesn't just sit there. It mobilizes.
“In some of those cases, we'll see, especially those ones that affect that brain stem component, because we have that sense of motion, you're going to get a ramp up of activity in the autonomic system, which may overfire or over mobilize energy in that system.”
The autonomic ramp-up you feel during a mast cell flare — the racing heart, the blood pressure swings, the heat intolerance — is the brain's attempt to manage a blood flow distribution problem. It's compensation, not a separate disease.
What This Means for Treatment
If mast cell activation is contributing to autonomic dysregulation by disrupting blood flow distribution, then:
- Treating the mast cell component may improve autonomic symptoms
- Treating the autonomic component may reduce the brain's stress response that can trigger mast cells
- Neither alone may be sufficient if both are feeding each other
The key is understanding the mechanism: which specific sympathetic pathways are involved, where blood is being redirected, and what the brain is responding to. Understanding how blood pooling works in POTS and what drives hyperadrenergic POTS can help clarify the picture.
Key Takeaways
- Sympathetic pathways are functionally distinct — skin and muscle sympathetic activity are different systems
- Histamine causes vasodilation in the skin — redirecting blood away from where the brain needs it
- MCAS flares can directly trigger POTS symptoms through blood flow redistribution
- The autonomic ramp-up is compensatory — the brain is trying to manage inadequate perfusion
- Both systems may need to be addressed since they feed each other
If you're dealing with both mast cell activation and autonomic dysfunction, understanding how small fiber neuropathy connects to dysautonomia may also be relevant to your case.
MCAS Flares Triggering Autonomic Symptoms?
If mast cell flares are driving your POTS symptoms and treating either condition alone isn't enough, a free consultation call can help identify the specific mechanism connecting them.
I'm Ready to Get Better