Last February, on a warm day in North Carolina, Dr. David Wohl entered the playground and saw his eight-year-old son, Zac, sitting motionless in the sandbox. “He looked like a 90-year-old guy who had fallen and couldn’t get up,” said Wohl, an AIDS expert and associate professor of infectious diseases at the University of North Carolina, Chapel Hill.
A few days later, after Zac was gripped by multiple intensive stomachaches, he was rushed to the hospital. “He was having 15 to 20 bellyaches a day. His grandmother could tell something was wrong by just looking at him,” Wohl said.
Zac was diagnosed with Crohn’s disease, a lifelong inflammatory bowel disease (IBD) that affects about 1.4 million Americans, most often Caucasians — and, even more often, Ashkenazi Jews. Studies have shown that as many as 317 of every 100,000 North Americans have Crohn’s disease, but among the Ashkenazi Jewish population, it is two to four times more prevalent. And for unknown reasons, it’s on the rise, among children in particular.
“Children under 18 [are] the fastest-growing patient population,” said Dr. Ted Densen, medical director of Cincinnati’s Children’s Hospital Medical Center’s Inflammatory Bowel Disease Center. “One in five children that are diagnosed with IBD present it with severe disease.” Symptoms can range from mild stomach pain and constipation to more severe aches, fatigue, diarrhea, bleeding and infection.
Although the doctors could diagnose Zac, they were unable to cure him: Crohn’s currently has neither a clear-cut cause nor a treatment. “IBD is not a one-size-fits-all disease,” said Dr. Sandra Kim, assistant professor of pediatrics at UNC School of Medicine and chair of pediatric affairs at the Crohn’s and Colitis Foundation of America. “Just because a treatment works on one kid does not mean it will have the same effects on another. Kids with IBD also have unique characteristics that are different from adults.”
With no standard path of treatment, Zac’s family was left with lots of decisions, none of them easy. “There was a lot of handwringing, because the doctor doesn’t tell you explicitly what you should do,” Wohl said. “She lays out all of the options, but you have to make the decision yourself. One of the drugs recommended to us carries the possibility of fatal lymphoma; another has toxic effects on child development. It was heart-wrenching.”
When Zac’s gastroenterologist, Kim, asked the family in April if they wanted to enroll Zac in a nationwide pediatric Crohn’s research study, Wohl did not hesitate. The study, known as the Pediatric RISK Stratification Project (RISK) — overseen by the Crohn’s and Colitis Foundation in partnership with 29 medical centers — is not testing a treatment. Rather, it is assembling, through blood and stool samples, the largest ever database of information from children with IBD. Since 2008, it has enrolled more than 1,740 children, with the goal of creating individualized patient profiles to better predict who is at risk for the severest form of the disease and which drugs will work best with whom. “The hope is that we can develop a model that will allow us to predict how a child’s disease will progress, or how they will respond to certain medications,” said Kim, who oversees the RISK study at UNC.
For many years, the only treatments for IBD were anti-inflammatory medications, such as sulfasalazine and mesalamine, which try to reduce symptoms by targeting the inflammation. But they often didn’t work well on the patients most severely affected and came with a plethora of side effects, such as nausea, diarrhea and insomnia. While corticosteroids remain a popular choice for short-term remission, pediatricians are particularly hesitant to prescribe them to adolescent patients because they can lead to stunted growth.
Another class of drugs, immunosuppressives, works by tamping down the immune system, thus alleviating the body’s fight against itself. Only one such drug, Purinethol is still regularly used, with varying levels of efficacy.
Alternatively, patients and their doctors try to control flair ups through special diets.
The most aggressive treatments are called biologics — intravenous infusions that target the immune system through a new mechanism: by binding to and suppressing a protein produced by the immune system known as Tumor Necrosis Factor (TNF). The anti-TNF biologic disables TNF in the bloodstream before it can damage the intestines. The infusion is administered every six to eight weeks and is a lifelong commitment: If you miss a treatment, the body may build up a resistance to the drug, rendering it ineffective.