Why These Three Conditions Often Travel Together
Introduction
If you’ve been diagnosed with hypermobile Ehlers-Danlos syndrome (hEDS), you may have noticed that your symptoms go far beyond just flexible joints. Maybe you get dizzy when you stand up. Maybe you break out in hives for no apparent reason. Maybe you have stomach problems, migraines, and fatigue that no one can explain.
You’re not imagining things. There’s a growing recognition in the medical community that three conditions frequently occur together: hypermobile Ehlers-Danlos syndrome (hEDS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). Doctors have started calling this combination “the triad.”
What Are These Three Conditions?
Hypermobile Ehlers-Danlos Syndrome (hEDS)
hEDS is a connective tissue disorder that affects the collagen in your body. Collagen is like the glue that holds your body together — it’s in your skin, joints, blood vessels, and organs.
In hEDS, this collagen is stretchier and more fragile than it should be. This leads to:
- Joints that bend further than normal (hypermobility)
- Frequent joint dislocations or sprains
- Chronic pain
- Easy bruising
- Soft, stretchy skin
- Fatigue
hEDS runs in families and is diagnosed based on clinical criteria, not genetic testing (unlike other types of EDS).
Postural Orthostatic Tachycardia Syndrome (POTS)
POTS is a form of dysautonomia — a malfunction of the autonomic nervous system, which controls automatic body functions like heart rate, blood pressure, and digestion.
In POTS, when you stand up, your heart rate increases dramatically (by 30 beats per minute or more) without a significant drop in blood pressure. This causes:
- Dizziness or lightheadedness when standing
- Rapid heartbeat
- Feeling faint
- Fatigue
- Brain fog
- Exercise intolerance
- Nausea
Mast Cell Activation Syndrome (MCAS)
MCAS occurs when mast cells — immune cells found throughout your body — become overly reactive and release their chemical contents too easily. This causes:
- Hives and flushing
- Swelling
- Stomach pain, nausea, and diarrhea
- Headaches
- Rapid heartbeat
- Feeling like you’re “allergic to everything”
How Common is the Triad?
Research shows these conditions overlap far more often than would be expected by chance:
- One study found that 31% of patients with both POTS and hEDS also had MCAS, compared to only 2% of patients without POTS and hEDS — an odds ratio of over 32.
- Another study found that 25% of women with hEDS had all three conditions — hEDS, POTS, and MCAS.
- In patients with MCAS and digestive symptoms, nearly 24% had EDS and 25% had POTS.
- More than half of women with hEDS report having POTS, and about one-third report having MCAS.
Why Do These Conditions Occur Together?
Scientists are still working to understand exactly why these three conditions travel together, but there are several theories:
The Connective Tissue Connection
In hEDS, the connective tissue throughout the body is abnormally stretchy. This affects:
- Blood vessels: Stretchy blood vessels may pool blood in the legs when you stand, triggering the heart rate increase seen in POTS.
- Mast cell environment: Mast cells live in connective tissue. When that tissue is abnormal, it may affect how mast cells behave, potentially making them more reactive.
Shared Nervous System Dysfunction
The autonomic nervous system — which is dysfunctional in POTS — also plays a role in regulating mast cells. When the autonomic nervous system isn’t working properly, it may contribute to mast cell instability.
Inflammation and Immune Dysregulation
Some researchers believe there may be underlying immune system abnormalities that contribute to all three conditions.
The Challenge of Diagnosis
One of the biggest challenges with the triad is that many doctors aren’t familiar with these conditions, especially MCAS. Patients often see multiple specialists over many years before getting diagnosed.
Common experiences include:
- Being told symptoms are “all in your head”
- Being diagnosed with anxiety or depression instead of POTS
- Being told you’re just “double-jointed” without recognizing hEDS
- Never having MCAS mentioned despite years of unexplained allergic-type symptoms
If you have one of these conditions, it’s worth being evaluated for the others. The symptoms overlap significantly, and treating all three can lead to much better quality of life.
Symptoms That Suggest You Might Have the Triad
Consider asking your doctor about the triad if you have:
- Flexible joints with frequent injuries since childhood
- Dizziness or rapid heartbeat when standing
- Chronic fatigue that doesn’t improve with rest
- Unexplained hives, flushing, or swelling
- Food intolerances that seem to change
- Stomach problems (nausea, cramping, diarrhea)
- Migraines
- Easy bruising
- Chronic pain
- Brain fog
- Family members with similar symptoms
Treatment Approaches
Because these conditions are interconnected, treatment often needs to address all three:
For hEDS:
- Physical therapy (especially aquatic therapy)
- Joint protection strategies
- Pain management
- Avoiding joint hyperextension
For POTS:
- Increased fluid intake (2-3 liters daily)
- Increased salt intake (8-10 grams daily)
- Compression stockings
- Gradual exercise programs
- Medications to help regulate heart rate and blood pressure
For MCAS:
- H1 antihistamines (like cetirizine)
- H2 antihistamines (like famotidine)
- Mast cell stabilizers (like cromolyn sodium)
- Leukotriene blockers (like montelukast)
- Trigger avoidance
- Carrying an epinephrine auto-injector for severe reactions
Many treatments help more than one condition. For example:
- Staying well-hydrated helps both POTS and MCAS
- Avoiding heat helps both POTS and MCAS
- Compression stockings help POTS and may reduce mast cell activation from blood pooling
Finding the Right Care
Managing the triad often requires a team approach. Helpful specialists may include:
- Allergist/Immunologist — especially one familiar with MCAS
- Cardiologist or Neurologist — for POTS evaluation
- Geneticist or Rheumatologist — for hEDS diagnosis
- Physical Therapist — preferably one experienced with hypermobility
- Gastroenterologist — for digestive symptoms
Look for providers who are familiar with these conditions and willing to coordinate care. Academic medical centers may have more experience with complex cases.
Living with the Triad
Living with hEDS, POTS, and MCAS can be challenging, but understanding that your symptoms are connected — and treatable — is empowering. Many patients report significant improvement in quality of life once all three conditions are properly diagnosed and managed.
Tips for living well with the triad:
- Pace yourself. Learn your limits and don’t push through symptoms.
- Stay hydrated and keep salt intake up. This helps both POTS and MCAS.
- Avoid known triggers. Keep a diary to identify patterns.
- Prioritize sleep. Poor sleep worsens all three conditions.
- Find support. Connect with others who understand what you’re going through.
- Advocate for yourself. You know your body best.
The Bottom Line
If you’ve been struggling with a constellation of symptoms that no one can explain — joint problems, dizziness, allergic reactions, stomach issues, fatigue — you may have the triad of hEDS, POTS, and MCAS.
These conditions are real, they’re connected, and they’re treatable. Don’t give up on finding answers. The right diagnosis can be life-changing.
References:
- Wang E, Ganti T, Vaou E, Hohler A. The Relationship Between Mast Cell Activation Syndrome, Postural Tachycardia Syndrome, and Ehlers-Danlos Syndrome. Allergy Asthma Proc. 2021;42(3):243-246.
- Aziz Q, Harris LA, Goodman BP, Simrén M, Shin A. AGA Clinical Practice Update on GI Manifestations and Autonomic or Immune Dysfunction in Hypermobile Ehlers-Danlos Syndrome: Expert Review. Clin Gastroenterol Hepatol. 2025;23(8):1291-1302.
- Collins Hutchinson ML, Liang E, Fuster E, Blitshteyn S. Autonomic Symptom Burden, Comorbidities and Quality of Life in Women With Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome. Auton Neurosci. 2025;262:103356.
- Mathias CJ, Owens A, Iodice V, Hakim A. Dysautonomia in the Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders — With a Focus on the Postural Tachycardia Syndrome. Am J Med Genet C Semin Med Genet. 2021;187(4):510-519.
- Yao L, Subramaniam K, Raja KM, et al. Association of Postural Orthostatic Tachycardia Syndrome, Hypermobility Spectrum Disorders, and Mast Cell Activation Syndrome in Young Patients. Front Neurol. 2025;16:1513199.
- Weiler CR, Austen KF, Akin C, et al. AAAAI Mast Cell Disorders Committee Work Group Report: Mast Cell Activation Syndrome (MCAS) Diagnosis and Management. J Allergy Clin Immunol. 2019;144(4):883-896.
