VEXAS 101

My journey with VEXAS began years before VEXAS even had a name.

My symptoms started around 2016, with recurring inflammation, painful skin lesions, fevers and overwhelming fatigue. In December 2017, I was diagnosed with histiocytoid Sweet’s syndrome (HSS). At the time, we were told it would likely progress to myelodysplastic syndrome (MDS) within about 18 months. And then we waited.

Eighteen months passed, then another year, and another. I didn’t develop MDS as expected, but I was far from well. For large stretches of those years, the fatigue was so debilitating that I was almost bedridden. Prednisone was the one thing that could reliably control the inflammation, but it came at a tremendous cost. I was dependent on steroids, sometimes at very high doses, for more than seven years. The years of prednisone left behind muscle, bone and other damage that I’m still dealing with today.

Then, in early 2023, I came across an article in a Sweet’s Syndrome Facebook support group about a newly discovered disease called VEXAS syndrome and it sounded exactly like what I had been experiencing.

I took the article to my doctors. At the time, testing wasn’t easy to find. They ultimately located a company in Germany that could test a saliva sample for the UBA1 mutation associated with VEXAS.

In June 2023, after years of searching for answers, I finally had a diagnosis: VEXAS syndrome.

Having a name for what was happening was an enormous relief. But it was also frightening. One of our first internet searches brought up information suggesting a 50% mortality rate within five years of diagnosis. After finally finding an answer, that was terrifying to read.

But the diagnosis also gave my doctors a new direction.

Eventually, I began treatment with azacitidine (Vidaza). Ironically, it was the same medication I likely would have received years earlier if the MDS we had been warned about in 2017 had become severe enough to require treatment.

Azacitidine hasn’t been easy. The cycles brought side effects, including a metallic taste, loss of appetite and difficulty maintaining my weight and strength. But for the first time, a treatment was addressing more than the symptoms.

After 16 cycles, blood testing could no longer detect my VEXAS-associated UBA1 mutation at the test’s reporting threshold. I am now considered to be in remission.

I know remission isn’t the same as a cure, and there are still health issues and unanswered questions. But I am in a very different place today.

Whenever I tell my VEXAS story, I have to talk about my wife too. She has been there through all of it, asking questions, documenting treatments and symptoms, pushing for medication approvals and helping manage the complexities of my care when I didn’t have the energy to do it myself. I know I’m not the only person with VEXAS who depends on someone they love to help them through this.

When I first became sick, VEXAS hadn’t even been discovered. Today, I am living in remission because researchers kept asking questions, physicians kept learning, patients shared information, and new treatment possibilities emerged.

That is what gives me hope for what comes next.

My name is Ian, and I have been diagnosed with VEXAS Syndrome.

My journey started in 2017 with some rather bizarre floating pains. One moment the pain would be in my thighs, then later in my ankles, shins or arms. At other times, it seemed to be everywhere. Around the same time, I suddenly started to suffer from tinnitus.

After a couple of months believing it would just clear up by itself, I saw my GP. That began years of appointments, blood tests and scans, but no answers. By 2018, I had become so frustrated that I decided to give up on the medical profession and just put up with it.

But as 2018 became 2019, then 2020, the symptoms kept increasing.

Sleep was almost impossible because of the pain, and the lethargy was intense. Getting ready for work required several rest periods, and I was no longer physically capable of doing my job as an Operations Controller for a large bus depot. I changed roles to become a roster clerk, which allowed me to work from home when required.

The breathlessness and lethargy continued to increase, to the point where I could no longer even walk to the staff cafeteria. My face became swollen, one eye was swollen shut, and I developed a purple rash from my neck to my shins. Still, I persisted until I collapsed at work in December 2023 and was admitted to Westmead Hospital in Sydney.

After weeks of testing, I was discharged without a diagnosis and with enough pills to choke a horse.

Still looking for answers, I saw a private rheumatologist who shared photographs of my symptoms with colleagues. One of those specialists recognised what he was seeing as possible VEXAS.

In March 2024, I finally had an explanation for what had been happening to me. Genetic testing that had been ordered months earlier came back and confirmed it: I was positive for VEXAS Syndrome, with a Met41Thr UBA1 variant and a VAF of 59%.

Treatment began with high-dose prednisolone and several steroid-sparing medications. Each time I tried to reduce the prednisolone below 20 mg, however, the VEXAS would flare and I would have to increase the dose again. My VAF had also risen to 73%.

Working together, my rheumatologist and haematologist recommended azacitidine.

The improvement since starting azacitidine has been dramatic. My prednisolone is now down to just 2 mg per day and continuing to decrease. My rash has disappeared, my blood work is almost normal and stable, and my VAF has fallen to 25%.

Most importantly, I feel so much better than before.

There is still a way to go, but I am hopeful about where things are heading.

If I could offer one piece of advice to someone else on this journey, it would be to advocate for yourself. VEXAS is still a very new disease, and there is still much being learned about how best to treat it. Do not blindly accept a specialist’s word for it. Ask questions and ask for the information they have. And if you are not happy with your treatment, find another specialist team. Finding the right specialist team made an enormous difference for me.