VEXAS - In Honor of Max Gyllenskog Part 1

Here's part 1 of a series I'm working on to try to help other people understand this disease as I'm learning it, in an easier way. I hope you will accept it. I'm working on more future parts as well. In honor of the best man I've ever known, Max Gyllenskog. It might sound like others you've read but I've seen very few out there. The more the better to try to spread awareness so hopefully other people can get it diagnosed as quickly as possible.

Max loved being considered a guinea pig for new treatments. In his case the short chemo didn't work fast enough but his family believes that if he had started it a year earlier, when he started showing serious symptoms he might still be alive today.
Please help us with project. Every doctor and hospital in the country and beyond need to learn about this so there won't be as many sad Max stories in the future.

VEXAS Syndrome is a rare disease that mainly affects middle-aged and older men. It's a genetic condition, but not one you're born with—it shows up later in life because of a change (mutation) in a gene in your bone marrow cells.

VEXAS is actually an acronym:
V = Vacuoles (tiny holes) in bone marrow cells
E = E1 enzyme (a protein that helps control inflammation)
X = The mutation happens on the X chromosome
A = Autoinflammatory (your immune system attacks your own body)
S = Somatic (the mutation happens during your lifetime—not inherited)

Symptoms of VEXAS include among other things:
- Long-term fevers
- Skin rashes
- Joint pain
- Swollen blood vessels
- Lung problems
- Low blood counts (causing fatigue, infections, or bruising)

Basically, the immune system is overactive and causes a lot of inflammation all over the body.
It’s caused by a mutation in a gene called UBA1. This gene helps control inflammation. When it’s mutated, the body can’t shut off inflammation properly, so the immune system stays in “attack mode” even when there’s no threat.

Think of it like a broken thermostat.
Imagine your immune system is like a home heater controlled by a thermostat.
Normally, the thermostat (the UBA1 gene) turns the heat (inflammation) on when it’s cold (when there’s an infection), and off when it’s warm (when the threat is gone).
But with VEXAS, the thermostat is broken.
It keeps the heater running all the time, even when it’s not needed. That constant heat causes damage throughout the house — just like chronic inflammation damages the body.

You could also think of your immune system as the fire department.
When there’s a fire (infection), they rush in to put it out—perfect!
But with VEXAS, the fire department keeps attacking even when there’s no fire.
They start spraying water on everything—your walls, your electronics, your furniture—just in case.
That’s what happens in VEXAS: the immune system is too aggressive, and ends up hurting healthy tissues.
It’s like your body thinks there’s a fire in your lungs and sprays the area with too many fire hoses. That excess fluid ends up flooding the lungs instead of helping.

The fire department analogy is a good example to describe how Max Gyllenskog died. The metaphoric water that the firemen wouldn't stop spraying kept flooding his lungs with liquid, making it harder and harder for him to breathe. His other organs are also getting damaged during this out of control attack on the body. Imagine sticking a high pressure sprayer down your throat and turning it on. Except it's not water, it's more like a toxic soup that your immune system has created in overdrive.

Meanwhile none of the doctors that were trying to treat him understood what was going on and kept misdiagnosing him with pneumonia. They kept thinking the fluid in his lungs was infection caused by bacteria, viruses or fungi, when in fact it's inflammatory fluid, which consists of:

- Immune cells - White blood cells that are overactive due to inflammation.
- Proteins & cytokines - These are chemical messengers that signal inflammation, causing blood vessels to leak.
- Plasma - Fluid from blood vessels.
- Sometimes red blood cells - If inflammation damages small blood vessels, blood can leak into the lungs.

Mixing all of those things together creates a type of toxic mud they call inflammatory fluid.
Inflammation makes tiny blood vessels "leaky," so fluid escapes into the lung tissue and air sacs. The more inflammatory fluid that gets inside the lungs the less room there is for air, and the harder and more painful it is to breathe. Also, filling the air sacs with fluid makes it hard for oxygen to get into the blood.

This all made Max feel short of breath, have low oxygen levels, chest tightness, and a terrible cough that never went away. Try blowing all of the breath out of your lungs and then cough without breathing in first.
It also damages other organs. Think of your kidneys as water filters cleaning your blood. Now imagine trying to filter muddy, toxic sludge full of inflammatory chemicals instead of water. The kidneys get clogged up and start to shut down. At the same time they are getting clogged up the toxic inflammatory liquid is also attacking the blood vessels that feed the kidneys and damages the supporting tissue. That’s what happens in VEXAS.

Symptoms You Might See while your kidneys are getting damaged:

- Swelling in the legs or face (from fluid buildup)
- Blood in urine
- High blood pressure
- Fatigue from poor kidney function

Other seriously infected organs (in more scientific terms)

Bone marrow - In VEXAS syndrome, the bone marrow is one of the central targets of the disease—and where the problem actually starts.

UBA1 Gene Mutation - The root cause of VEXAS is a somatic mutation in the UBA1 gene, which is critical for protein recycling in blood-forming (hematopoietic) stem cells in the bone marrow. This mutation causes these cells to malfunction and trigger excessive inflammation throughout the body.
The bone marrow starts producing abnormal white blood cells that are hyper-inflammatory. These abnormal cells release cytokines (inflammatory messengers), damaging the bone marrow and other organs.

VEXAS can cause multiple blood cell lines to decrease:

- Anemia (low red blood cells): fatigue, weakness, shortness of breath
- Thrombocytopenia (low platelets): bleeding, bruising
- Leukopenia (low white blood cells): infection risk (less common)

Sometimes it can cause bone marrow failure. VEXAS turns the bone marrow into a factory of inflammation, producing defective immune cells that spread damage throughout the body. It can lead to low blood counts, immune system overload, and serious complications if not treated.

In easier to understand terms:
Your bone marrow is like the factory inside your bones that makes all your blood cells — red cells that carry oxygen, white cells that fight infection, and platelets that help you stop bleeding.
In VEXAS syndrome, something goes wrong right at the source. A mistake (called a mutation) happens in a gene called UBA1, which is like a set of instructions that helps your blood cell factory run smoothly. When this gene is broken, the bone marrow starts making defective white blood cells.
These bad white blood cells act like they’re stuck in “attack mode.” They send out way too many inflammation signals, like a fire alarm that won’t shut off. This creates massive inflammation not just in the bone marrow, but all over the body.

Because of this:

Your bone marrow may stop making enough red blood cells, which can make you feel tired or short of breath (this is called anemia).
It may not make enough platelets, so you bruise or bleed more easily.
Sometimes you get fewer white blood cells, making it harder to fight off infections.
In serious cases, the whole blood-making system can shut down — kind of like the factory going on strike — which is called bone marrow failure.

So, in short:
VEXAS messes with the bone marrow, causing it to create broken immune cells that spread inflammation and lower your healthy blood cell counts. If not treated, it can cause big problems all over your body.
Joints and Cartilage

In VEXAS, your immune system goes kind of haywire and starts attacking parts of your own body — including your joints (like knees, fingers, elbows) and cartilage (the flexible stuff in your ears, nose, ribs, and between bones).

Think of it like this: Normally, your immune system is like security guards that fight off germs. In VEXAS, those guards get confused and start attacking your own joints and cartilage by mistake — like setting off alarms for no reason and smashing up your own stuff.

Because of this, you might feel:

- Pain, especially in places that bend or move a lot (like fingers, knees, or shoulders). Swelling, redness, and warmth in joints
- Stiffness, especially in the morning or after resting
- Tenderness in your ears or nose, which can get swollen or misshapen over time

This kind of inflammation can look like arthritis or a rare condition called relapsing polychondritis (which literally means cartilage that keeps getting inflamed over and over again).

This was among one of the first symptoms that affected Max. His ears would swell up, which made them hard and extremely painful. He couldn't sleep on either of his sides because of the agonizing pain. Then it started happening to his nose as well. These symptoms would come and go over time.

Central Nervous System

Your central nervous system is your brain and spinal cord — kind of like the command center of your body. It controls how you think, feel, move, and everything else your body does automatically. In VEXAS, the immune system can go rogue and start attacking blood vessels in the brain and spinal cord. This is called vasculitis — basically, inflammation of blood vessels.

So what does that do? When the blood vessels in your brain are inflamed, your brain might not get enough oxygen or nutrients. That can cause:

- Headaches that don’t go away
- Confusion or trouble thinking clearly
- Speech problems or slurred words
- Seizures
- Weakness or numbness in parts of your body
- Feeling like you’re not quite yourself — mentally or emotionally

In serious cases, it can even look like a stroke, which is when part of the brain doesn’t get enough blood and shuts down temporarily or permanently.

Heart

Your heart is like the engine of your body—it keeps everything running by pumping blood 24/7. But in VEXAS syndrome, your immune system gets confused and starts messing with that engine.
- Inflammation Around the Heart (Pericarditis) - The heart has a little “jacket” around it called the pericardium. In VEXAS, that jacket gets inflamed, so your heart feels tight or squeezed. It can cause chest pain, especially when you breathe in or lie down.
- Heart Muscle Inflammation (Myocarditis) - Sometimes VEXAS attacks the heart muscle itself, making it weaker. That can lead to tiredness, shortness of breath, or feeling like your heart is racing or skipping beats.
- Heart Rhythm Problems (Arrhythmias) - The inflammation can mess with your heart’s electrical system, causing weird rhythms. You might feel like your heart’s doing backflips or beating way too fast or slow.
VEXAS makes your immune system go into overdrive. It starts attacking blood vessels and tissues—even inside the heart. This causes pain, swelling, and sometimes long-term damage if it’s not treated.
Think of it like your immune system thinks there’s a fire in the heart—even though there isn’t—so it shows up with water hoses and drenches the engine. That ends up flooding and damaging the heart, even though it was fine to begin with. VEXAS can cause inflammation in and around your heart, which leads to chest pain, shortness of breath, weird heartbeats, and tiredness. It’s your immune system attacking the wrong thing—again.

Liver
Your liver is like your body’s filter and chemical lab. It cleans out bad stuff, helps digest food, stores energy, and even makes important proteins. But when you have VEXAS, your immune system thinks the liver is the bad guy — and starts attacking it for no reason.
Liver Inflammation (Hepatitis) - Your immune system causes the liver to get swollen and irritated. That’s called autoimmune hepatitis when it happens from your body attacking itself. You usually don’t feel it at first, but over time it can cause fatigue, nausea, stomach pain and jaundice.

High Liver Enzymes - Doctors check for "liver enzymes" in blood tests — if they’re high, it’s a sign your liver is under attack. It’s kind of like your liver sending out SOS signals in your blood. Scarring Over Time (Fibrosis or Cirrhosis). If the attack keeps going and isn’t treated, the liver gets scarred, like a bruise that won’t heal. Too much scarring makes the liver stop working well — that’s serious.

What’s Actually Happening:
- VEXAS makes white blood cells go rogue and inflame healthy organs.
- In the liver, that causes the tiny blood vessels and liver cells to get damaged.
- It’s like throwing a party in your liver with way too many angry guests — and things get broken.

Think of It Like:
Your liver is the janitor and lab technician of your body. But in VEXAS, the security guards (your immune system) kick down the door, accuse the janitor of crimes, and start trashing the lab instead. VEXAS makes your immune system attack your liver by mistake, causing inflammation, high liver enzymes, fatigue, and even liver damage if it goes untreated.

Skin

Imagine your immune system is like a bunch of over-caffeinated security guards. In VEXAS, these guards think everything is a threat—even your skin—so they start attacking it by mistake. That causes inflammation, which makes your skin freak out.
- Painful red bumps or rashes - You might see bright red spots, welts, or bruised-looking patches. These aren’t just normal pimples or allergies—these hurt and can spread.
- Feels hot and swollen
- The skin can feel warm, itchy, or sore, like it’s sunburned from the inside.
- Can turn into sores or ulcers.
- Some people get open wounds or blisters if the inflammation gets really bad.
- They can leave marks or scars.
- It keeps coming back. You treat it, it gets better, then boom—it flares up again. It’s like your skin is stuck in a never-ending game of “why are you mad now?”

Eyes
Eye Inflammation (like swelling or burning inside your eye). The body sends too many immune cells to the eyes. That causes pain, redness, and light sensitivity — kind of like having really bad pink eye, but it's from inflammation, not an infection.
- Uveitis: is the inflammation deep inside the eye (can mess with vision).
- Scleritis: is the white part of your eye gets super red and painful.
If inflammation isn’t treated, it can lead to blurry vision, eye pressure, or even vision loss over time. It's like your eyes are fogged up or out of focus, even though there's nothing wrong with your glasses.
VEXAS makes your body’s immune system overreact, and when that happens to your eyes, they can get red, sore, and sensitive — and your vision can suffer. Doctors usually treat it with steroids or immune-suppressing meds to calm things down.

Doctors might suspect VEXAS if someone has:
- Mysterious inflammation
- Bone marrow problems
- Doesn't respond well to usual treatments
- They can confirm it with genetic testing of the UBA1 gene.
There is no cure yet, but treatments can help control symptoms. These include:
- Steroids (to calm inflammation)
- Immune-suppressing drugs
- In some cases, bone marrow transplants

Doctors are still learning a lot about VEXAS—it was only discovered in 2020!
VEXAS was discovered by scientists at the NIH (National Institutes of Health) using new genetic tools. It’s one of the first diseases found by looking backward from mysterious symptoms instead of starting with family history.

The VEXAS Foundation notes an average diagnosis delay of 5.5 years. We've got a lot of work to do.