Hi Friend
In Part 1 I introduced you to mast cells and explained why MCAS is so frequently missed by conventional medicine. If you missed it, check your inbox for last week's email.
Today I want to tell you something that changes the picture for a lot of people. Something that explains why so many patients with MCAS spend years going round in circles, seeing specialist after specialist, trying treatment after treatment, and never quite getting better.
The reason is almost always the same.
They are not dealing with one condition. They are dealing with three.
The Triad
There is a cluster of three conditions that co-occur together so frequently and so consistently that researchers and specialist clinicians now refer to them as a triad. The three conditions are Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome or POTS, and Hypermobile Ehlers-Danlos Syndrome or hEDS.
If you have one of these conditions there is a significant chance you have at least one of the others. And if you have all three, which is far more common than most doctors realise, treating any single one of them while ignoring the others will always produce incomplete results at best and no results at worst.
Let me explain what each condition is and crucially why they are so deeply interconnected.
POTS - The Condition That Explains Your Dizziness, Racing Heart, and Brain Fog
Postural Orthostatic Tachycardia Syndrome is a form of dysautonomia, which means the autonomic nervous system, the part of your nervous system that controls heart rate, blood pressure, blood vessel tone, digestion, and dozens of other automatic functions, is not working properly.
In POTS specifically the problem is that when you stand up, your heart rate rises excessively, typically by more than 30 beats per minute within ten minutes of standing, because your blood vessels are not constricting properly to push blood back up to your brain and heart against gravity. The result is that blood pools in your lower body when you are upright, your brain becomes relatively underperfused, and you feel dizzy, light-headed, breathless, exhausted, and mentally foggy in ways that are dramatically worse when standing or after exertion.
The symptoms of POTS are remarkably easy to dismiss or misattribute. The dizziness gets labelled as anxiety. The rapid heartbeat gets investigated by cardiology and called benign. The profound fatigue gets dismissed as deconditioning. The brain fog gets told it is stress. Sound familiar?
POTS affects an estimated one million people in the UK, the vast majority of whom are undiagnosed.
hEDS - The Condition That Explains Your Joint Pain, Injuries, and Why Your Body Feels Unstable
Hypermobile Ehlers-Danlos Syndrome is a heritable connective tissue disorder. Connective tissue is essentially the scaffolding of your body. It holds everything together, from your joints and ligaments to your blood vessel walls, your gut, your skin, and your nervous system sheathing. In hEDS this connective tissue is too lax, too stretchy, insufficiently supportive.
The most obvious manifestation is hypermobility, joints that bend further than they should. But hEDS is not just about being bendy. The consequences of lax connective tissue throughout the body are far reaching. Joints that sublux or dislocate. Chronic pain from joints that are not properly supported. Gut dysmotility because the gut wall lacks normal tone. Bladder problems. Easy bruising. Skin that stretches unusually or scars poorly. Fatigue from the constant muscular effort required to compensate for inadequate ligamentous support.
Most people with hEDS have never been given that diagnosis. They have been told they are just flexible, or clumsy, or that their pain is fibromyalgia, or that their gut problems are IBS. The average time to diagnosis of hEDS is ten years.
Why These Three Conditions Travel Together
This is the part that most doctors do not understand and that changes everything when you do.
The three conditions share overlapping biological mechanisms that mean having one creates the conditions for having the others.
Mast cells are present in connective tissue throughout the body. In hEDS the connective tissue is structurally abnormal. There is good evidence that structurally abnormal connective tissue is associated with abnormal mast cell behaviour, essentially the mechanical instability of hEDS creates an environment in which mast cells become dysregulated. This is why so many hEDS patients also have MCAS.
Mast cells are also densely distributed around blood vessels and in the perivascular tissue that controls vascular tone. When mast cells activate they release mediators including histamine that directly cause vasodilation and alter blood vessel tone. Dysregulated mast cells in a body with already lax blood vessel walls from hEDS create exactly the vascular instability that characterises POTS. This is why so many MCAS patients also have POTS.
And of course POTS and hEDS are deeply connected because the same connective tissue laxity that causes joint instability in hEDS also affects the blood vessel walls, reducing their ability to constrict normally on standing. Lax blood vessel walls plus pooling blood plus dysregulated mast cells releasing vasodilatory mediators equals the POTS phenotype.
The three conditions reinforce and perpetuate each other. Mast cell activation worsens vascular instability. Vascular instability worsens fatigue and cognitive symptoms. Poor connective tissue support worsens pain and further destabilises mast cells. Treating one without addressing the others is like trying to empty a bath without turning off the tap.
Long Covid and The Triad
I want to add one more piece to this picture because it is increasingly important and affects millions of people.
Long Covid, meaning ongoing symptoms following SARS-CoV-2 infection persisting beyond twelve weeks, has a symptom profile that overlaps almost entirely with the MCAS and POTS clinical picture. The fatigue, the brain fog, the post-exertional malaise, the cardiovascular symptoms, the gut problems, the neurological symptoms, the immune dysregulation, these are the hallmarks of both Long Covid and MCAS plus POTS.
The emerging scientific consensus is that for a significant proportion of Long Covid patients, the viral infection has triggered or dramatically worsened pre-existing but perhaps subclinical mast cell dysregulation and autonomic dysfunction. The virus essentially unmasked or activated the triad in people who may have had a genetic predisposition to it without having previously met the threshold for symptoms severe enough to seek medical attention.
This means that many Long Covid patients are not dealing with a purely post-viral syndrome. They are dealing with newly activated or worsened MCAS and POTS that existed at a subclinical level before their infection. The treatment implication is significant. Treating them as purely post-viral patients, focusing only on rest and pacing, without addressing the underlying mast cell and autonomic components, is likely to produce much slower and less complete recovery than treating the MCAS and POTS directly.
What This Means For You
If you have been diagnosed with one of these conditions but not the others, it is worth asking whether the full picture has been properly explored.
If you have been told you have fibromyalgia, chronic fatigue syndrome, IBS, or anxiety, it is worth asking whether any of these three conditions has ever been assessed.
If you have Long Covid and your recovery feels stuck despite doing everything right with pacing and rest, it is worth asking whether MCAS and POTS treatment might be the missing piece.
The good news, and there is real and genuine good news here, is that when you treat the triad as a whole rather than as separate unconnected problems, the results can be remarkable. Antihistamines reduce mast cell mediator burden. POTS management improves cerebral blood flow and reduces fatigue and brain fog. Connective tissue support through targeted physiotherapy and lifestyle adjustments reduces pain and joint instability. And the knock-on effects of each treatment help the others work better.
This is exactly the approach we take at Mend Clinic. Not treating your gut and ignoring your heart rate. Not treating your skin reactions and ignoring your joint pain. Treating the whole person as a connected biological system.
Coming Up In Part 3
Next week I am going to take you through the diagnostic journey. How MCAS is actually diagnosed. Why your normal blood tests do not rule it out. What tests are actually useful. And why the response to treatment is itself one of the most powerful diagnostic tools available. This is the email where the pieces really start to come together.
As I mentioned at the end of last week's email, I am very close to launching a new low cost service that will allow you to find out whether your symptoms could be consistent with MCAS. More details are coming very soon. If you want to be first to know when it launches, simply reply to this email with the word READY and I will make sure you hear about it before anyone else.
Stay Well
Disclaimer
The content in this newsletter is for educational and informational purposes only and does not constitute medical advice, diagnosis, or treatment. The information provided is intended to support, not replace, the relationship between you and your own healthcare professional. Always seek the advice of your GP or another qualified healthcare provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read in this newsletter. Mend Clinic accepts no liability for any decisions made based on the content of this newsletter. If you are experiencing a medical emergency please call 999 or attend your nearest accident and emergency department immediately.
