Life Of Riley: A Peculiar Pattern, An Aha Moment And A Lifesaving Label

This is the third installment in a special CommonHealth/WBUR series, The Life of Riley: A Rare Girl, A Rare Disease. It’s the story of a remarkable nine-year-old girl born with a one-in-a-million disease that creates increasingly aggressive “lumps and bumps” on and in her body. The only treatment, so far, has been surgery. But right now, at Children’s Hospital Boston, Riley is trying an experimental drug that may—or may not—help her.

Last week, Riley went in for the 32nd MRI of her young life. The stakes were high: If there was a significant new growth on her spine, she might be knocked off the Children’s clinical trial—and possibly face another operation.

The news is good: The MRI showed that her spine looked “stable.” Riley and her family rejoiced but did not celebrate. Kristen Davis, Riley’s mother, emailed: “It’s kind of sad that we didn’t celebrate but we are all very guarded in terms of our hopefulness about this news.”

This week, we explore the genesis of CLOVES, Riley’s disease, and how one doctor’s obsessive talent for pattern recognition ended up helping her and many others.

The patients all shared certain peculiar features with no obvious link: Lumps in the back. Left leg bigger than right leg, or some other asymmetry. Unusually shaped feet. Flaws in the formation of their veins or arteries, known as vascular anomalies. Mole-like spots on their skin, or “port wine”-colored stains.

These patients are different, Dr. Ahmad Alomari recalls thinking. Different from others, but somehow alike.

He wrote his observations on slips of paper and they accumulated in his office, among the piles containing thousands of other notes. A radiologist at Children’s Hospital Boston, Dr. Alomari is known for having an extraordinary eye for patterns. But this pattern wouldn’t quite gel.

So just before he was due to take a leave in mid-2006, he effectively locked himself into an empty lab room and began to look at images of the hospital’s vascular anomalies patients. Thousands upon thousands of images. He would set down his cup of coffee on his desk by 6 in the morning and close the door. He would not eat; he would barely leave his seat, until he went home at 8 or 9 in the evening. His colleagues joked that they should pass him in food under the door.

This single-minded self-confinement went on for more than a month. Ultimately, what came from it was a new diagnosis with the power to save lives.

Images of Riley Cerabona, then a pre-schooler who had already needed repeated surgeries to remove large benign growths from her torso and a lesion from her back, were among those that Dr. Alomari provisionally called Peculiar Pattern 1, or PP1.

When Riley was eventually diagnosed with CLOVES, the full implications of finally having a label were not immediately clear to her parents. But it was a comfort and a call to action, said Kristen Davis, Riley’s mother: “Now we have a name for this, and let’s find other people who have this.”

When you have a label you can understand what to expect. You’re not just floating out there with some weird thing.
 “When you have a label you can understand what to expect—maybe,” she added. “Or at least have some guidelines about what to do. You’re not just floating out there with some weird thing.”

The number of known rare diseases has been growing by the thousands in recent years. When Vice President Mary Dunkle first began working at the National Organization for Rare Disorders in 1999, the party line was that “there were 5,000 diseases affecting 20 million Americans,” she said. “Then it went up to 6,000 diseases affecting 25 million people and now it’s nearly 7,000 diseases affecting nearly 30 million Americans.”

Francis Collins, director of the National Institutes of Health, told the organization last year that the science of rare diseases has never moved faster.

There are many examples of how getting the right diagnosis can help patients with rare diseases, Ms. Dunkle said. One rare disease is easily mistaken for multiple sclerosis, but needs different treatment. A potentially fatal disorder that causes internal swelling can be treated and even prevented with the right drugs, but an attack may be mistaken for a simple allergic reaction.

Science tends to be a highly collective enterprise, but in the world of rare diseases, a disorder is often named after the individual doctor who first identified it. For patients to meet that doctor, Ms. Dunkle said, is “almost sometimes for us like meeting a rock star.”

If CLOVES has a rock star, that would be Dr. Alomari, and his promoter would be Children’s Hospital Boston surgeon Dr. Steven Fishman, who for a while was calling the disorder “Alomari Syndrome.”

A bit of background: The Vascular Anomalies Center at Children’s, which Dr. Fishman co-directs, is renowned as one of the best in the world, and its late scientific director, the widely revered Dr. Judah Folkman, was famed for his work on trying to stop cancers by cutting off their blood supply.

Because its staff sees patients from all over the world, Dr. Fishman said, “You get to see rare things commonly,” and that helps patterns come clear. He quotes Dr. Folkman, his mentor: “Cherish your exceptions.” Those patients who don’t follow the rules may teach you the most.

Dr. Fishman recalls: For a long time, Riley’s condition had been known as a PUVA (pronounced poo-va, and meaning a Provisionally Unique Vascular Anomaly.) It was clear that her growths were unusual—he performed the surgery himself to remove them—but not that they were part of a syndrome.

We looked at each other and said, ‘Oh, yeah, these all sort of look the same.’

Then one day, “Dr. Alomari asked me if he could make a presentation at our Wednesday night conference, which we have to review patients from around the world. He said, ‘Can I take ten minutes? I want to show you guys something.’ I said, ‘Sure, any time, Ahmad.’”

Dr. Alomari presented a Power Point series of images showing 18 patients, including Riley, with his “Peculiar Pattern 1.” One after another came the growths on the torso, the skin stains, the oddly shaped feet.

‘It was really an ‘Aha’ moment, it was his ‘Aha’ to us,” Dr. Fishman said. “We looked at each other and said, ‘Oh, yeah, these all sort of look the same.’ And eventually Ahmad and another group at the National Institutes of Health put together two series of patients” with what would eventually be called CLOVES.

The moral of the story, from Dr. Alomari: “If you believe in something, even if you have no evidence of it, it’s a dogma based on one or two encounters, just continue looking for the evidence and work hard to find the evidence, and at one point you may find it.”

What difference does a diagnosis make if it’s so rare only 80 or 100 people have it? As a surgeon, Dr. Fishman knows all too well.

Now that CLOVES is a known entity, he said, patients who are diagnosed with it can be warned about the type of blood-vessel malformations in the spine that have posed a major threat to Riley. Their spines can be carefully imaged by vigilant doctors.

With their abnormal blood vessels, CLOVES patients are also now known to be at risk for pulmonary embolisms, dangerous blood clots that tend to break off in the legs and go to the lungs.

Once that was recognized, Dr. Fishman said, surgeons doing operations on CLOVES patients could give them blood-thinners and use filters to prevent or stop the clots.

But even then, bizarrely, some patients still got clots to their lungs. It was Dr. Alomari, he said, who recognized that “maybe these aren’t coming from the legs where pulmonary embolisms usually come from. It turns out patients with CLOVES have large abnormal veins in their chests and sometimes in their arms.” With that knowledge, surgeons can now guard against those clots as well.

We can improve clinical care by knowing what to watch for.

Just in the last few months, the CLOVES diagnosis has yielded yet more important knowledge: Patients appear to be at heightened risk for a rare kidney cancer known as Wilms’ tumor, which tends to be treatable if caught early.

The bottom line, Dr. Fishman said, is: “We can improve clinical care by knowing what to watch for.”

He thinks, he said, about a girl from Italy whom he operated on perhaps 17 years ago, to remove a huge fatty mass from her shoulder. After surgery, she developed a blood clot in her arm vein, and it ended up breaking off and going to her lungs.

“She arrested. We realized what happened, and I opened up her chest, her heart,” but it was too late; she had severe brain complications and never recovered. Now, it would be clear that she had CLOVES, but this was long ago.

“If we saw that patient today, we would predict the possibility of that clot,” he said. “I can’t bring her back. I wish I could. But at least the next time I see one, which I do all the time, we can take all the precautions and get the same benefit with much less risk.”

Please follow our community rules when engaging in comment discussion on this site.
  • Joy2bjoy

    I am a 53yr old woman who has lived with a right side deformity all my life where the right side of my body is visibly larger  than the left side,some told me it was ‘something hereditary’,some said it was ‘one of those things’ some referred to me as’ a freak of nature’ the lumps and bumps on my toes were supposedly because my mother bought me ill fitting shoes as a young child,my large fingers must have been broken in the past thus leaving them fat and flat.
    Until this week, when I went to see Dr Huson in Genetics medicine at Manchester University Hospital no one has ever been able to understand or explain why my body is like it is,Dr Huson and her medical students explained such a lot to me  which I found fascinating,she guided me to the Cloves Syndrome web site and I identify with some stories I have read here.
    I look forward to seeing more of Dr Huson and her team and will do all I can with further tests etc to help these amazing people who have chose to study and specialise in this field.

  • Chris

    Thank you for this wonderful, uplifting story. I’m humbled by the humanity, dedication and brilliance of these doctors.

  • Anonymous

    This is a good example of why hate and prejudice are so wasteful and ridiculous. If haters saw this this man on the street and heard his first name, they would be willing to see him dead or jailed. We would again lose a beautiful mind. How many have we lost already and how many more do we have to lose befoer the hating stops? Thank you Dr. Ahmad Alomari!!

  • Gretchenohalloran

    you guys are the best of the brilliant in thinking outside of the box.  thank you!

  • Kristen Davis

    So delighted to see so many people reading and being inspired by Riley’s story – she is our rock star!!  To directly impact the quality of life for people with CLOVES, please share these stories to help us spread awareness for our loved ones,  or consider a tax deductible financial donation to http://www.clovessyndrome.org or http://www.clovesfoundation.org 

    • Guest

       Thank you for your bravery and Good Luck. Give Riley my best, please.

    • Trisha

      Hello — Just listening to Riley’s story and  wondering if she would like to go on an uplifting sail that we will coordinate for her and her guests this summer? Our new non-profit is “Sailing Heals” (www.sailingheals.org). There is no charge at all. Please be in touch if you think Riley and her guests would enjoy this spirit-lifting day at sea! We would love to host Riley and the team that keeps her going!