The hEDS/POTS/MCAS Triad

Understanding the hEDS–POTS–MCAS Overlap

If you’ve been diagnosed with hypermobile Ehlers-Danlos syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), or Mast Cell Activation Syndrome (MCAS)—or you suspect one of them—you may have noticed something important:

These conditions rarely show up alone.

Many people live for years with confusing, shifting symptoms before realizing they’re experiencing an overlap of connective tissue, autonomic nervous system, and immune dysregulation. This post breaks down what each condition is, why they commonly coexist, and what this means for diagnosis, care, and daily life.

What Is hEDS?

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder affecting collagen—the protein that provides structure and stability throughout the body.

Because connective tissue is everywhere, hEDS is not just about joint hypermobility.

Common features include:

  • Joint hypermobility, instability, and frequent subluxations

  • Chronic pain and early-onset musculoskeletal issues

  • Fragile or stretchy skin

  • Poor wound healing or easy bruising

  • Fatigue and exercise intolerance

Connective tissue also plays a key role in blood vessels, the gastrointestinal tract, and organ support, which helps explain why people with hEDS often experience symptoms far beyond their joints.

What Is POTS?

Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia—a disorder of the autonomic nervous system.

POTS is characterized by an abnormal heart rate increase upon standing, but its impact is much broader.

Common symptoms include:

  • Rapid heart rate, palpitations, or dizziness when upright

  • Lightheadedness or fainting

  • Brain fog and cognitive fatigue

  • Heat intolerance

  • Exercise intolerance

  • Gastrointestinal symptoms

  • Adrenaline surges or anxiety-like sensations

In people with hEDS, lax connective tissue can affect blood vessel tone, allowing blood to pool in the lower body when standing. This can worsen or directly contribute to POTS symptoms.

What Is MCAS?

Mast Cell Activation Syndrome (MCAS) involves inappropriate or excessive activation of mast cells—immune cells involved in allergic responses, inflammation, and tissue repair.

Unlike classic allergies, MCAS reactions may occur without a clear trigger and can affect multiple systems at once.

Common symptoms include:

  • Flushing, itching, or hives

  • Gastrointestinal distress (nausea, diarrhea, cramping)

  • Food and medication sensitivities

  • Headaches or migraines

  • Blood pressure changes

  • Shortness of breath or throat tightness

  • Fatigue and brain fog

Mast cells live in connective tissue and interact closely with the nervous system—making MCAS particularly relevant in people with hEDS and POTS.

Why Do hEDS, POTS, and MCAS So Often Coexist?

1. Shared Connective Tissue Dysfunction

Connective tissue abnormalities in hEDS can:

  • Reduce blood vessel stability → contributing to POTS

  • Alter the environment mast cells live in → promoting inappropriate activation

2. Nervous System–Immune Crosstalk

The autonomic nervous system and immune system constantly communicate. Dysregulation in one can amplify dysfunction in the other, creating a feedback loop of symptoms.

3. Mast Cells and the Nervous System

Mast cells release mediators (like histamine and prostaglandins) that can:

  • Affect heart rate and blood pressure

  • Increase nerve sensitivity

  • Worsen orthostatic intolerance

This means MCAS flares can directly intensify POTS symptoms.

4. Diagnostic Fragmentation

These conditions are often treated in isolation by different specialists. Without a whole-body lens, the underlying pattern may be missed—leading to delayed or incomplete diagnosis.

What the Overlap Feels Like in Real Life

People with the hEDS–POTS–MCAS triad often describe:

  • Symptoms that shift day to day

  • Reactions that seem disproportionate or unpredictable

  • Feeling dismissed because tests look “normal”

  • Needing to manage posture, food, stress, temperature, and pacing simultaneously

This is not a failure of resilience—it’s a reflection of complex, multi-system physiology.

Why a Whole-Body, Systems-Based Approach Matters

Because these conditions influence one another, care is most effective when it is:

  • Interdisciplinary (rather than siloed)

  • Symptom-pattern–based, not just test-based

  • Nervous-system informed

  • Pacing- and capacity-focused, not push-through

Support may include a combination of:

  • Autonomic regulation strategies

  • Joint stabilization and safe movement

  • Mast cell–aware nutrition and medication planning

  • Stress and sensory load management

  • Education and self-advocacy support

You’re Not “Too Complex”

If you live at the intersection of hEDS, POTS, and MCAS, your body isn’t broken—it’s communicating.

Understanding the overlap helps:

  • Reduce self-blame

  • Improve diagnostic clarity

  • Support more sustainable care plans

  • Validate lived experience

Healing doesn’t mean fixing everything at once. It means learning how your systems interact—and responding with curiosity, compassion, and appropriate support.

If you’d like help navigating this overlap, building a sustainable care plan, or understanding your symptoms through a nervous-system–informed lens, you don’t have to do it alone. Book a free consultation with me to see if working together can help you make progress in your health journey!

Book a Free consultation here!
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If You Can’t Connect the Issues, Think Connective Tissues