Click Here to Download this Blog Post – The “Why” Behind The Pain (Part 13)

By Dr. Nicholas L. DePace, M..D., F.A.C.C – Cardiologist specializing in autonomic dysfunction, Ehlers-Danlos syndrome and POTS.

Many people spend years—sometimes decades—bouncing between doctors, trying to explain two persistent problems: constant dizziness and chronic pain.

If you have been diagnosed with hEDS (Hypermobile Ehlers-Danlos Syndrome) or HSD (Hypermobility Spectrum Disorder), these aren’t just random bad luck. There is a specific chain of command causing your symptoms, and understanding it is the first step to managing it.

The Chain Reaction: From Tissue to Nerves to Pain

It is helpful to think of your condition as a domino effect. Here is how the medical literature explains the sequence:

1. The Root Cause: You have hEDS or HSD. This means your connective tissue (the glue holding your body together) is built differently.
2. The Middleman: Because your tissue is “stretchy” or loose, it interferes with your P&S (Parasympathetic and Sympathetic) Nerves. As we discussed in the previous post, this causes your body’s “autopilot” to glitch.
3. The Symptom: This nerve dysfunction leads to Orthostatic Dysfunction (dizziness and fainting when standing). Crucially, these nerve glitches also amplify pain. The pain isn’t just in your joints; your nervous system is turning the volume knob up, making everything hurt more.

What Doctors Should See: The Physical Clues

When a doctor looks at your history and performs a physical exam, they shouldn’t just be looking at your heart rate. They should be looking at you.

In patients with these disorders, the body tells a story through four main physical signs:

• Super-Stretchy Skin (Hyperextensibility): Your skin might pull away from your body much further than the average person’s, almost like elastic.
• Over-Flexible Joints (Hypermobility): You can bend your fingers, elbows, or knees past the “normal” stopping point.
• Fragile Tissue: Your skin might tear easily or heal poorly.
• Easy Bruising: You might find mysterious bruises without remembering how you got them, because the blood vessels under the skin are fragile.

A Critical Warning: The “Vascular” Variety

While hEDS is the most common form, there is a rarer, more dangerous cousin called Vascular EDS (vEDS).

The medical community often misses this diagnosis until it is too late—usually after a major, life-threatening event. Because vEDS affects the blood vessels and organs directly, it requires different attention.

The Red Flags for Vascular EDS If you or a family member have a history of the following, especially if it happened before age 40, it is vital to check for vEDS:

• Organ Rupture: A history of intestines or other organs tearing or rupturing unexpectedly.
• Aneurysms: Bulges in blood vessels.
• Major Bleeding: Bleeding that is difficult to stop or happens spontaneously.

The Takeaway: If you have easy bruising combined with a family history of sudden organ trouble or aneurysms at a young age, do not wait. This specific history is the loudest alarm bell for doctors to investigate Vascular EDS immediately.

Where to Seek Expert Care?

It is important to seek out a clinician with expertise in EDS to make an accurate diagnosis and create a treatment plan. One of the nation’s leading centers is Franklin Cardiovascular Associates, under the direction of Nicholas DePace, MD, FACC. They are located in Sicklerville, New Jersey. franklincardiovascular.com, (856) 589-6034

About the Author

Nicholas L. DePace, MD, FACC is a board-certified cardiologist and Medical Director of Franklin Cardiovascular Associates. A graduate of the Mount Sinai School of Medicine, Dr. DePace has decades of clinical, academic, and research experience and has held faculty appointments as a Clinical Professor of Medicine, becoming one of the youngest full professors in Philadelphia at the time of his appointment.

Dr. DePace specializes in the diagnosis and treatment of autonomic nervous system dysfunction (dysautonomia), including POTS, autonomic dysfunction associated with Ehlers-Danlos syndrome (EDS), chronic fatigue, and anxiety-like conditions that are frequently misdiagnosed. He is nationally recognized for his work on parasympathetic and sympathetic (P&S) nervous system imbalance, a core mechanism underlying many complex chronic disorders.

In addition to treating patients from across the United States, Dr. DePace is a prolific clinical researcher and author of multiple nationally distributed medical textbooks published by Springer and W.W. Norton, focusing on autonomic dysfunction, mitochondrial disorders, cardiovascular disease, and mind–body medicine.

👉 View Dr. DePace’s professional profile
👉 View medical books by Dr. DePace

Click Here to Download this Blog Post – The Body’s Overactive Security System: Understanding Mast Cell Activation Syndrome (MCAS) (Part 11)

By Dr. Nicholas L. DePace, M..D., F.A.C.C – Cardiologist specializing in autonomic dysfunction, Ehlers-Danlos syndrome and POTS.

The Body’s Overactive Security System: Understanding Mast Cell Activation Syndrome (MCAS)

If you have been diagnosed with a connective tissue disorder like hEDS or HSD, you might feel like your symptoms go far beyond just “loose joints.” You might struggle with random flushing, stomach issues, brain fog, or reactions to foods that seem to change day by day.

The culprit might not be your joints, but your Mast Cells.

In many of our patients, the immune system and the nervous system are engaged in a chaotic dance. This leads to a condition called Mast Cell Activation Syndrome (MCAS). Here is how it works and why it happens.

What Are Mast Cells? The “First Responders”

Think of Mast Cells as the security guards of your body. They are immune cells born in your bone marrow that travel to almost every tissue in your body. They sit and wait for trouble—like bacteria, viruses, or an injury.

When they spot a threat, they “degranulate.” This means they explode open and release a cocktail of chemicals, including histamine, heparin, and other protectors. This process causes inflammation to help you heal and changes your blood flow to get help to the injury site.

When the Guards Go Rogue: What is MCAS?

In a healthy person, mast cells only react to real threats. In patients with MCAS, these cells become overactive and confused. They start viewing harmless things—like certain foods, smells, or stress—as dangerous invaders.

When they overreact, they dump massive amounts of chemicals into your system, causing a wide range of symptoms:

• Skin: Flushing, hives, itching.
• Breathing: Wheezing, stuffy nose, throat tightness.
• Heart: Racing heart (tachycardia), low blood pressure, fainting.
• Stomach: Nausea, vomiting, diarrhea, cramping.
• Head: Brain fog, headaches, migraines.

The Missing Link: The Nervous System Connection

You might wonder: Why are my immune cells freaking out?

The answer often lies in your P&S Nervous System (Parasympathetic and Sympathetic).

1. The Manager (Parasympathetic): This system is supposed to control and coordinate your immune system.
2. The Trigger (Sympathetic): This system tells the mast cells to release their chemicals.

In patients with hEDS/HSD, the P&S system is already dysfunctional. If the “Manager” isn’t doing its job and the “Trigger” is too sensitive, your mast cells end up releasing histamine constantly. This worsens your dizziness (dysautonomia) and pain.

How Do We Diagnose It? The “Rule of Three”

Diagnosing MCAS can be tricky because symptoms come and go. We look for three specific criteria:

1. Clinical Symptoms: You must have symptoms in two or more body systems (e.g., skin and stomach) that happen repeatedly.
2. Lab Tests: We look for elevated levels of specific chemicals (like Tryptase or Histamine) in your blood or urine. Note: These can sometimes show up normal if you aren’t having an active flare-up or are already taking meds.
3. Response to Treatment: If we treat you with mast cell stabilizers or antihistamines and you get better, that is a strong sign you have MCAS.

The Genetic Clue: HaT

Some patients have a specific genetic trait called Hereditary Alpha-Tryptasemia (HaT). This is a duplication of a gene that causes high levels of Tryptase. It is commonly linked to hEDS, MCAS, and autonomic dysfunction. A simple DNA swab can test for this.

Treatment: Locking Both Doors

The most common treatment involves blocking the histamine that is making you miserable. However, you can’t just take one type of allergy pill.

Your body has different “doors” (receptors) that lets histamine in. To get relief, you usually need to block both:

• H1 Blockers: These are your standard allergy meds (like Zyrtec, Xyzal, or Benadryl).
• H2 Blockers: These are often sold as heartburn meds (like Pepcid).

If you only block one, the histamine just uses the other door!

The Bottom Line

MCAS is essentially an “allergy” to things you aren’t actually allergic to, driven by a nervous system that has lost its rhythm. It explains why so many hEDS patients also have IBS, food sensitivities, and random allergic reactions.

By calming the nervous system and stabilizing these cells, we can often turn down the volume on these symptoms, helping you feel more in control of your body.

Where to Seek Expert Care

It is important to seek out a clinician with expertise in EDS to make an accurate diagnosis and create a treatment plan. One of the nation’s leading centers is Franklin Cardiovascular Associates, under the direction of Nicholas DePace, MD, FACC. They are located in Sicklerville, New Jersey. franklincardiovascular.com, (856) 589-6034

About the Author

Nicholas L. DePace, MD, FACC is a board-certified cardiologist and Medical Director of Franklin Cardiovascular Associates. A graduate of the Mount Sinai School of Medicine, Dr. DePace has decades of clinical, academic, and research experience and has held faculty appointments as a Clinical Professor of Medicine, becoming one of the youngest full professors in Philadelphia at the time of his appointment.

Dr. DePace specializes in the diagnosis and treatment of autonomic nervous system dysfunction (dysautonomia), including POTS, autonomic dysfunction associated with Ehlers-Danlos syndrome (EDS), chronic fatigue, and anxiety-like conditions that are frequently misdiagnosed. He is nationally recognized for his work on parasympathetic and sympathetic (P&S) nervous system imbalance, a core mechanism underlying many complex chronic disorders.

In addition to treating patients from across the United States, Dr. DePace is a prolific clinical researcher and author of multiple nationally distributed medical textbooks published by Springer and W.W. Norton, focusing on autonomic dysfunction, mitochondrial disorders, cardiovascular disease, and mind–body medicine.

👉 View Dr. DePace’s professional profile
👉 View medical books by Dr. DePace

Click Here to Download this Blog Post – It’s Not “All in Your Head”—It’s Lack of Blood Flow to Your Head (Part 10)

By Dr. Nicholas L. DePace, M..D., F.A.C.C – Cardiologist specializing in autonomic dysfunction, Ehlers-Danlos syndrome and POTS.

How hEDS and HSD Symptoms Connect to the P&S Nervous System

If you have hEDS (Hypermobile Ehlers-Danlos Syndrome) or HSD (Hypermobility Spectrum Disorder), you are likely used to dealing with pain and loose joints. But for many patients, the symptoms that actually disrupt daily life the most—brain fog, anxiety, racing hearts, and stomach issues—seem completely unrelated to their joints.

The truth is, they are directly connected through your P&S Nervous System (Parasympathetic and Sympathetic systems).

When you have hEDS, your “hardware” (your heart, brain, and stomach organs) is usually perfectly healthy. The problem is the “software” (the nerves telling them what to do) is glitching. Here is how that glitch works.

The Two Main Glitches in hEDS and HSD

Most hEDS patients suffer from two specific types of nervous system dysfunction:

1. Sympathetic Withdrawal (The “Failure to Squeeze”)

Normally, when you stand up, your Sympathetic nerves (fight or flight) tell your blood vessels to squeeze tight to push blood up against gravity. In hEDS patients, these nerves often fail to react—we call this Sympathetic Withdrawal.

• The Result: Gravity wins. Blood pools in your legs.
• The Consequence: Your heart, brain, and arms don’t get enough blood flow. This leads to profound fatigue, fainting, and cold hands.

2. Parasympathetic Excess (The “Over-Reaction”)

Your Parasympathetic system is supposed to be your “Rest and Digest” mode. However, in hEDS patients, this system often overreacts to stress.

• The Result: Instead of calming you down, it amplifies pain signals and disrupts your digestion.
• The Consequence: This leads to GI issues (stomach paralysis or urgency), bladder issues, and a heightened sensitivity to pain.

The “Great Masquerader”: Why It Looks Like Anxiety or Heart Disease

Because of Sympathetic Withdrawal, your brain and heart are constantly starved of the blood flow they need to function optimally. This leads to symptoms that mimic other serious diseases, leading to misdiagnoses.

The “Heart Attack” Mimic

When your heart isn’t getting enough blood flow because it’s pooling in your legs, it races and pounds to try to compensate.

• Symptoms: Chest pain, palpitations, shortness of breath.
• The Reality: Patients are often terrified they have heart disease, but the heart muscle is healthy. It’s just working overtime because of the blood flow issue.

The “Mental Health” Mimic

When the brain doesn’t get enough blood flow (poor cerebral perfusion), it starts misfiring. This is perhaps the most validating discovery for many patients.

• Symptoms: Brain fog, inability to focus, mood swings, and panic.
• The Misdiagnosis: These symptoms often look exactly like Anxiety, Depression, Bipolar Disorder, OCD, or ADD/ADHD.
• The Reality: While these conditions can coexist, often the “anxiety” or “attention deficit” is actually the brain panicking because it isn’t getting enough oxygen and fuel. Even unexplained seizures can sometimes be traced back to this lack of blood flow.

 A Note on Safety: The Vascular EDS Distinction

While we focus heavily on the quality of life for hEDS patients, we must always keep an eye out for Vascular EDS (vEDS).

As mentioned in previous posts, vEDS is the rare, life-threatening form. Unlike the “bendy” hEDS patients who faint and hurt, vEDS patients are defined by tissue fragility.

• The Clue: If a patient (especially under 40) has a history of organ rupture (like intestines), aneurysm, or severe bleeding that goes beyond simple bruising, we must suspect vEDS.
• The Distinction: hEDS is about pain and dizziness. vEDS is about tissue fragility and bleeding.

The Path Forward for hEDS/HSD Patients

The most important takeaway is this: Your organs are likely healthy.

The treatment for hEDS/HSD isn’t about fixing a “broken” heart or a “broken” brain. It is about fixing the P&S nerve signals. Through proper testing, we can prove that your organs are fine, which is reassuring!

Once we know it’s a “software” issue, we can create a personalized plan to help your nerves communicate better, keeping your blood where it belongs: in your head and heart.

Where to Seek Expert Care

It is important to seek out a clinician with expertise in EDS to make an accurate diagnosis and create a treatment plan. One of the nation’s leading centers is Franklin Cardiovascular Associates, under the direction of Nicholas DePace, MD, FACC. They are located in Sicklerville, New Jersey. franklincardiovascular.com, (856) 589-6034

About the Author

Nicholas L. DePace, MD, FACC is a board-certified cardiologist and Medical Director of Franklin Cardiovascular Associates. A graduate of the Mount Sinai School of Medicine, Dr. DePace has decades of clinical, academic, and research experience and has held faculty appointments as a Clinical Professor of Medicine, becoming one of the youngest full professors in Philadelphia at the time of his appointment.

Dr. DePace specializes in the diagnosis and treatment of autonomic nervous system dysfunction (dysautonomia), including POTS, autonomic dysfunction associated with Ehlers-Danlos syndrome (EDS), chronic fatigue, and anxiety-like conditions that are frequently misdiagnosed. He is nationally recognized for his work on parasympathetic and sympathetic (P&S) nervous system imbalance, a core mechanism underlying many complex chronic disorders.

In addition to treating patients from across the United States, Dr. DePace is a prolific clinical researcher and author of multiple nationally distributed medical textbooks published by Springer and W.W. Norton, focusing on autonomic dysfunction, mitochondrial disorders, cardiovascular disease, and mind–body medicine.

👉 View Dr. DePace’s professional profile
👉 View medical books by Dr. DePace

Click Here to Download this Blog Post – The Hidden Danger: Why We Look for Vascular EDS (vEDS) (Part 9)

By Dr. Nicholas L. DePace, M..D., F.A.C.C – Cardiologist specializing in autonomic dysfunction, Ehlers-Danlos syndrome and POTS.

When people hear “Ehlers-Danlos Syndrome” (EDS), they usually picture someone who is extremely flexible, double-jointed, or has stretchy skin. While that is true for the most common type (hEDS), there is a much rarer form of the condition that doctors must watch for carefully: Vascular Ehlers-Danlos Syndrome (vEDS).

While the common hypermobile type (hEDS/HSD) can cause pain and fatigue, it is generally considered “benign” regarding life span—meaning patients live a normal length of life.

Vascular Ehlers-Danlos Syndrome (vEDS) is different.

It is a life-threatening condition that affects the body’s internal structures rather than just the joints. Because it carries a high risk of severe complications and a shorter average life expectancy (often into the 40s), diagnosing it early—before an emergency happens—is critical.

It Doesn’t Look Like “Normal” EDS

The trickiest part of diagnosing Vascular EDS is that it breaks the rules of what we think EDS looks like.

• Skin: Unlike the common types, vEDS patients usually do not have stretchy (hyperextensible) skin.
• Joints: These patients are usually not hypermobile in their large joints (like knees or elbows). They might have some flexibility in small joints (like fingers), but they generally don’t pass the “party trick” flexibility tests.

Because they don’t look “bendy,” they often fly under the radar until something goes wrong. This is why heightened awareness is so important.

The Red Flags: Family History and Warning Signs

Since we can’t rely on loose joints to spot vEDS, we have to look at medical history and family history.

If you or a family member have a history of the following, it is a major red flag that requires immediate investigation:

1. Unexplained Ruptures: A history of blood vessels bursting or organs rupturing (such as the bowel/intestines) without a clear cause.

2. Vascular Dissections: This is when the layers of a blood vessel tear apart.
3. Aneurysms: Weak spots in arteries that balloon out.
4. Severe Bleeding: Bleeding tendencies that go far beyond just “easy bruising.”
5. Complications in Childbirth: Abnormal tissue healing or severe complications during labor or gynecological procedures.

Why Vascular Ehlers-Danlos Syndrome (vEDS) Diagnosis Can’t Wait?

With the common hypermobile type of EDS, diagnosis is about managing quality of life. With Vascular EDS, diagnosis is about saving a life.

Knowing a patient has vEDS changes how doctors treat them entirely. It allows us to monitor the blood vessels and take precautions to prevent ruptures. If there is a family history of sudden vascular issues or significant bleeding abnormalities, we do not wait—we test.

It is important to seek out a clinician with expertise in EDS to make an accurate diagnosis and create a treatment plan. One of the nation’s leading centers is Franklin Cardiovascular Associates, under the direction of Nicholas DePace, MD, FACC. They are located in Sicklerville, New Jersey. franklincardiovascular.com, (856) 589-6034

About the Author

Nicholas L. DePace, MD, FACC is a board-certified cardiologist and Medical Director of Franklin Cardiovascular Associates. A graduate of the Mount Sinai School of Medicine, Dr. DePace has decades of clinical, academic, and research experience and has held faculty appointments as a Clinical Professor of Medicine, becoming one of the youngest full professors in Philadelphia at the time of his appointment.

Dr. DePace specializes in the diagnosis and treatment of autonomic nervous system dysfunction (dysautonomia), including POTS, autonomic dysfunction associated with Ehlers-Danlos syndrome (EDS), chronic fatigue, and anxiety-like conditions that are frequently misdiagnosed. He is nationally recognized for his work on parasympathetic and sympathetic (P&S) nervous system imbalance, a core mechanism underlying many complex chronic disorders.

In addition to treating patients from across the United States, Dr. DePace is a prolific clinical researcher and author of multiple nationally distributed medical textbooks published by Springer and W.W. Norton, focusing on autonomic dysfunction, mitochondrial disorders, cardiovascular disease, and mind–body medicine.

👉 View Dr. DePace’s professional profile
👉 View medical books by Dr. DePace