The Children’s Crusade

Turning research into treatments for patients with ”orphan diseases.”
At CCHMC there are departments devoted to dozens of unfamiliar conditions and disorders.

Illustration by Adam Hancher

One of the first things you notice when you get to Cincinnati Children’s Hospital Medical Center are the signs. Before you experience the swell of medical professionals all around, before you even comprehend the children in wheelchairs, you’re reading signs. They lead you through the maze of the parking garage, the bank of elevators, the welcome desks. And then you’re looking at departmental signs—prominent boards hanging from the ceiling, proclaiming conditions that read like the cast of characters in a parent’s nightmare: Emergency. Nephrology. Cancer and Blood Diseases. There are other signs you might not see, though—smaller signs in offices tucked away inside bigger departments. These signs don’t inhabit parents’ nightmares; not because the diseases aren’t terrible, but because they aren’t part of our vernacular. Many have exotic, difficult-to-pronounce names, like Fanconi anemia, Ehlers Danlos syndrome, and diffuse intrinsic pontine glioma, which Lauren Hill, a student at Mount St. Joseph, elevated onto the national stage. At CCHMC there are departments devoted to these and dozens of other unfamiliar conditions and disorders. If you know, or worse, love someone who’s been diagnosed with one of those strange-sounding diseases, you understand how the strangeness quickly becomes familiar, how all too soon those syllables fall out of your mouth as easily as memorized lyrics or an overused cliché. And you come to appreciate CCHMC’s commitment to giving the patients who have these diseases—and their families—the care and support they need.


For the DiGiovanna family, the once-exotic term that’s become a household name is “epidermolysis bullosa,” better known as EB. Sixteen-year-old Shane was born with EB, which means his skin is missing a protein, making it extremely fragile and prone to blistering and shredding. There’s no cure or even a real treatment, other than to swathe a child in bandages to try to protect the wounds and keep fingers and toes from webbing. The DiGiovannas are fierce in their efforts to help raise funds and awareness: Shane advocates for EB research through public speaking and sharing his story on various websites; dad Chuck sells his own seasoning concoction called “Dad Salt”; and the whole family throws a polar bear plunge each New Year’s morning, convincing scores of people to jump into their icy suburban pool in Montgomery and into Long Island Sound in Connecticut, near where they used to live. To date, their efforts have raised upwards of $70,000.

But if you ask Shane what he and his family have done to most improve his quality of life, he’d tell you it was relocating to Montgomery—or re-relocating, since they’d lived here once before—where they have ready access to CCHMC’s EB Center, which sees patients from around the world. He describes their time in Connecticut, from 2005 to 2010, as the “dark years”—a comment that’s perhaps part teen drama, part black humor, and part fact. Those were the years when they sought care at countless hospitals throughout Connecticut, New York, and Massachusetts, only to find that each institution lacked physicians experienced with EB. “We tried a bunch of different hospitals,” Shane said, “but none of them had seen more than maybe one or two EB patients at most.” After a year in Connecticut, Shane and his mother, Patsy, began commuting back to Cincinnati whenever he needed surgery, which was frequently. In 2009, the year before the whole family moved back, Shane and Patsy toured New England medical facilities, visiting 14 new physicians, searching for the elusive Holy Grail of EB expertise. “We tried hard to make it work,” Patsy said, “but it was this crazy life, running around there looking for doctors and traveling back here for surgeries. It was really hard, especially on Meggie,” Shane’s younger sister. “We were looking all over for doctors, and the whole time our doctors were sitting here, waiting for us.”

Those doctors are a team, headed by Anne Lucky, pediatric dermatologist and medical director of the EB Center. The team spans about 25 specialties, ranging from surgery to dentistry to urology to pain management. Although programs like the EB Center—highly specialized centers for rare genetic diseases—are unusual in the world at large, they’re fairly common within the walls of CCHMC.


Technically speaking, when separating out pediatric cases, most childhood diseases fall into the category of a rare disease, which is defined as fewer than 200,000 patients in the U.S. But even within that definition, this hospital is known for both its breadth and depth of work in little-known diseases, sometimes called “orphan diseases” because they haven’t been “adopted” by pharmaceutical companies or the medical community. Orphan diseases have received more attention in recent years thanks to a combination of smart advocacy on the part of families, coordinated efforts by groups like the National Organization for Rare Disorders, venture capital investment, and FDA incentives for sponsors who develop therapies for rare conditions. Yet knowledgeable, accessible, expert care for many diseases remains, even in many top institutions, as rare as the diseases themselves. According to Margaret Hostetter, chair of pediatrics and director of the CCHMC research foundation, a major pediatric institution might typically have around 10 clinics devoted to rare genetic disorders, but it is difficult to quantify exactly how many Cincinnati Children’s has due to the proliferation of sub-specialties in the building. “If you said somewhere around 50, it wouldn’t be viewed as a wild exaggeration,” she says.

The fact that one of the top children’s hospitals in the country would take on a greater-than-average number of rare diseases is hardly a shocker. But a fivefold increase? Why so many? Hostetter says it’s because the hospital is unique in its size, its resources, and especially, its will to invest in new discovery. It also speaks to the hospital’s commitment to genetic research, because the underlying source of most rare diseases is, by and large, genetic. “It’s not necessarily that we see more rare diseases or take them more seriously, but we have the expertise here to help understand the root causes of many of them,” Hostetter said.

That’s not just an insider’s perspective. Industry has embraced the hospital as a leader in rare diseases; in 2013 it was featured as a “world-class” institution at the biotech Rare Disease Partnering Summit in Chicago, and more recently, Alexion Pharmaceuticals, which focuses on developing transformative therapies for rare, life-threatening diseases, established a Rare Disease Innovation Fund within the hospital’s broader Innovation Fund. This year’s call for proposals just concluded; although only the Alexion award is specifically earmarked for a rare disease, over half of all applications received—23 out of 45—could help in the area of rare diseases, said Chris Stahl, business development manager for Children’s Hospital’s Center for Technology Commercialization. That revelation was, he said, a confirmation rather than a surprise. “We’ve always suspected there was a significant amount of research in the rare disease space in this institution, and this is proof of it.” It’s also proof, Hostetter says, of the hospital’s commitment to having research and treatment go hand-in-hand. “A lot of hospitals say, ‘We’re here to do the treatment,’ and others say, ‘We just want to invent new treatments.’ In this place, it’s all connected. It’s our research and discovery that enable us to develop new treatments that then improve our outcomes for patients.”


How that plays out can be seen through the EB Center’s mix of scientific discovery and patient care. In its 10 and a half years, the center has had 25 papers published in peer-reviewed journals, has developed a genetic diagnostic tool for EB that’s identified two mutations other labs missed, and one doctor currently has an application under consideration for the first Alexion Rare Disease Innovation Fund award. At the same time, the center is clearly focused on its patients. If EB is an orphan disease, the EB Center strives to provide the best foster care possible. You can see that in full display at the periodic clinics the center runs. While new EB patients are seen weekly at the hospital, the tightly coordinated clinic materializes one Thursday each month, in the Multi-practice Center on the second floor of Location C. It’s an unassuming place, with examining rooms on either side of a small central office, where physicians, nurses, a nurse-practitioner, and the center coordinator overlap. The office here operates something like an air traffic control tower, with a board showing which room each patient is in, which doctors they’ll see, and in what order. Depending on the moment you look at the board, slots may be open or may be crossed off. It’s finely crafted choreography, completely patient-centered; rather than having the children, who are stripped of their copious bandages, move from specialist to specialist, the doctors cycle in and out of the rooms. “It’s interdisciplinary, not just one-stop shopping,” said Lucky, who cofounded the center with Richard Azizkhan, surgeon-in-chief, in 2004. “After the evaluation, the team communicates, and we have one document that goes out. As medical director, I review it to make sure there’s no huge discrepancy that would confuse the family. We don’t have to agree on everything, but we try to have one voice.”

The care extends outside of the hospital, too. Lucky and her staff spend large chunks of their day in phone and e-mail contact—coordinating care with other hospitals, fielding questions from nurseries about newborns with EB, doing follow-up with patients, and addressing families’ questions and concerns. The bulk of the 75–100 patients the center sees each year come from outside the Cincinnati area, so that level of communication is vital. It was a lifeline for the DiGiovannas when they were in Connecticut, providing the single best source of medical and emotional support they had. “I could call them and talk for an hour about anything, and they’d answer every question I had, tell me all of these things I should look out for,” Patsy DiGiovanna said. “These people are taking care of an incurable, untreatable condition. There are no successes here. They’re just an amazing, incredible team.”

If that level of attention sounds remarkable, it is. But it’s not unique to the EB Center. The prototype for these specialized rare disease programs at the hospital was the Aerodigestive Center, which serves patients with a host of complex airway disorders. That model was so effective that the rest seemed to grow organically: the Hemangioma and Vascular Malformation Program for children with abnormal blood vessels, the Velopharyngeal Insufficiency Clinic for particular kinds of speech dysfunction, the Congenital Diaphragmatic Hernia Team for infants with a complex intestinal and lung complication—the list goes on. If those names are hard to pronounce, if they’re too foreign-sounding for you to remember, count yourself lucky. They probably don’t affect anyone in your life. But if they’re distressingly familiar to you and you live around Cincinnati, some might say you’re lucky, too. At least you’ll have someone nearby who can translate the language and guide you on the journey. And that, coupled with whatever state-of-the-art treatment exists, just might be the rarest kind of care around.

Originally published in the May 2015 issue.

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