The University of Chicago Medicine - Comer Children's Hospital

Department of Pediatrics 2017 Annual Report

Genomics & Organ Physiology Gastroenterology, Hepatology & Nutrition

Stefano Guandalini, MD, with patient Sofia Cruz

Gluten-free kids with celiac disease have GI symptoms resolve in 24 months

Patient Maeve O’Grady and her parents meet with Hilary Jericho, MD

Children with celiac disease who strictly adhere to a gluten-free diet (GFD) can expect resolution of their gastrointestinal symptoms within 24 months—a better outcome than adults with celiac disease, according to a recent study by Hilary Jericho, MD, MSCI, along with authors Naire Sansotta, MD, Stefano Guandalini, MD, and Karine Amirikian, MD, published in the Journal of Pediatric Gastroenterology and Nutrition. The retrospective chart review of 227 children and 327 adults from the University of Chicago Celiac Disease Center database found that among children who adhered to a GFD, 90 percent had resolution of their gastrointestinal symptoms, and a smaller proportion (87 percent) had resolution of extra-intestinal symptoms, such as short stature, fatigue and headaches. In comparison, 86 percent of adults who remained faithful to a GFD no longer had gastrointestinal symptoms, and 80 percent had resolution of extra-intestinal symptoms during the study’s two-year follow-up.

“Most kids with gastrointestinal symptoms from celiac disease, roughly 78 percent of our study’s pediatric population, do very well on a gluten-free diet, and they tend to have better adherence than adults because their parents are guiding what they eat,” says Jericho. “Females, however, reported lower rates of improvement in gastrointestinal symptoms than males, which may be related to hormones or genetic predisposition.” Also, children with longer duration of symptoms and those who were not adherent to a GFD had ongoing symptoms. In addition, children with extra-intestinal manifestation of celiac disease showed less improvement of their symptoms. “Whereas gastrointestinal symptoms tend to resolve when gut inflammation is reduced by not eating gluten, extra-intestinal symptoms involve a more complex pathway and take longer to resolve,” she says.

The study’s results give clinicians and parents a time frame on which to base expectations for symptom improvement after a child begins a GFD. “Some kids’ symptoms will disappear in weeks, but many need a longer period on a gluten-free diet, especially if they have long-standing symptoms or extra-intestinal manifestations,” says Jericho. The study also provides a benchmark for clinicians to conduct additional diagnostic tests if a child isn’t improving. “If a prepubescent child continues to have short stature after following a GFD for two years, it’s important to look for other comorbidities, such as Turner’s syndrome or inflammatory bowel disease,” she says. 

A career spent focusing a spotlight on celiac disease

Stefano Guandalini, MD, with patient Charles Philip Atteberry

When Stefano Guandalini, MD, joined the faculty of the University of Chicago in 1996, very few children were diagnosed with celiac disease—a dramatic difference from his native Italy, where he treated scores of infants and young children with celiac disease at the University of Naples. Since then, he has led a passionate crusade to not only raise awareness of celiac disease (CD) among pediatric gastroenterologists in the United States, but also to establish guidelines for clinical care and diagnosis, and to advance research toward a cure, a dream Guandalini predicts will be realized within a decade.

In 2001, Guandalini launched the University of Chicago Celiac Disease Center and began rectifying the rampant under-diagnosis of CD by creating intensive educational courses at the University of Chicago for medical professionals and by lecturing around the world. In the last 15 years, he has imparted his knowledge of CD to more than a half million clinicians, parents and patients.

Guandalini’s vision was for the center to also become a premier CD research institution. “Dr. Guandalini was instrumental in raising funds that allowed novel, groundbreaking discoveries to come to fruition and ultimately to attract multiple NIH grants,” says Carol Shilson, executive director of the Celiac Disease Center. “We are so much closer to a cure because of discoveries that have occurred here.”

Guandalini has been tireless in motivating physician-scientists and researchers to study celiac disease and improve the lives of patients with the disease. He founded the North American Society for the Study of Celiac Disease, which supports the research of young investigators. As one of the foremost clinicians on celiac disease in the world, he has trained many young gastroenterologists to become celiac experts. Now professor emeritus of pediatrics and chief of the Section of Pediatric Gastroenterology, Hepatology and Nutrition, Guandalini remains dedicated to the promise of curing celiac disease and continues to see pediatric patients in clinic, speak at international meetings and raise funds for ongoing research.

“The world owes a debt of gratitude to Stefano Guandalini for his ardent pursuit of raising awareness of celiac disease and promoting screening and research,” says John M. Cunningham, MD, chair of the Department of Pediatrics. “He has improved the lives of countless patients and has shared his expertise with numerous physicians, while never wavering in his belief that a cure for celiac disease is possible.”

Identifying children who will benefit from early, intensive treatment of Crohn's

Barbara Kirschner, MD

The most efficacious drugs for treating severe, progressive forms of pediatric Crohn’s disease (CD) are also among the most expensive. Anti-tumor necrosis factor α (TNFα) agents can cost thousands of dollars per dose, but 20 percent of children given these drugs to prevent complications don’t respond. In addition, there are no validated models to predict which children with CD are at risk for complications and might, therefore, be candidates for earlier anti-TNFα therapy.

“We want to predict the subset of children who will develop severe, progressive disease so we can administer treatment earlier and more intensively than what would otherwise be indicated,” says Barbara Kirschner, MD, Professor Emerita of Pediatrics and Medicine. “However, we don’t want to give the therapy to children who won’t benefit from it or to children who make antibodies to the protein, which may render the drug ineffective should they need it later.”

Kirschner was the Comer Children’s site principal investigator on a large, collaborative, prospective inception cohort study of 913 newly diagnosed children with CD conducted at 28 centers in the United States and Canada. Of these children, 9 percent experienced CD complications—either stricturing, in which the bowel wall becomes thickened, rigid and narrow, leading to bowel obstruction, or penetrating disease resulting in fistulas due to inflammation, ulceration and perforation in the bowel wall.

The study, published in The Lancet in April 2017, was designed to better understand the pathogenesis of pediatric CD and the precise mechanisms responsible for disease complications. “Routine clinical and laboratory tests currently used to predict severity of disease, such as age of onset, ileal disease location and serological responses to certain microbial antigens, had a sensitivity of only 66 percent,” says Kirschner.

But when the researchers examined ileal gene expression patterns in the affected gut, they found that extracellular matrix pathways were induced in children with stricturing complications, while mitochondrial respiratory chain genes were protective against stricturing. In contrast, genes associated with the acute inflammatory response to microbes such as bacterial flagellin (CBir1) were associated with penetrating disease. “These novel ileal gene signatures may, in the future, allow us to risk-stratify patients at diagnosis and identify those who will respond to therapy,” says Kirschner. “And by demonstrating potential differences in disease pathogenesis for stricturing and penetrating complications, we’ve identified that an antifibrotic approach may be beneficial in patients at high risk for stricturing complications.” In contrast, children who received early anti-TNFα therapy, defined as within 90 days of diagnosis, had only one-third the frequency of penetrating complications, but the drugs had no effect on reducing stricturing.

Conditions We Treat


Academic Appointments

  • Associate Professor of Pediatrics
    Director, Pediatric Hepatology
    Medical Director, Pediatric Liver Transplant Program

  • Associate Professor of Pediatrics
    Acting Chief, Gastroenterology

  • Professor Emeritus of Pediatrics
    Founder and Medical Director, Celiac Disease Center
    Chief, Pediatric Gastroenterology, Hepatology, and Nutrition

    Named a Top Doctor in 2018 by Chicago magazine

  • Professor of Medicine and Pediatrics
    Director, Celiac Disease Research

  • Assistant Professor of Pediatrics
    Director, Pediatric Celiac Disease Research

  • Professor Emerita of Pediatrics and Medicine

  • Assistant Professor of Pediatrics

  • Associate Professor of Pediatrics
    Director, Pediatric Nutrition Support Service
    Director, Pediatric Gastrointestinal Endoscopy

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