Gianna presented to CHOP’s Division of Gastroenterology at 8 years of age with a 16 lb weight loss over 1 year. She was having abdominal pain associated with eating. Her weight, however, at presentation was at the 90th percentile and her height was 25th percentile. Her screening blood work included Hgb 12.5, MCV 69.3, and an ESR 41. Her albumin was 3.5. She had a history of hemorrhoids and had seen blood in her stool only once. On physical exam, her abdomen was soft, nontender, and without organomegaly. She had a large skin tag visible on perianal exam, and her stool was hemoccult negative on rectal exam. She underwent an upper GI series with small bowel follow through that was normal. Upper endoscopy and colonoscopy demonstrated esophagitis, chronic antritis, focal acute duodenitis, and diffuse inflammation in the terminal ileum, with mucosal granulomas confirming the diagnosis of Crohn’s disease.
Over the next 4 years, Gianna underwent various escalating medical therapies, but initial improvement was followed by a return of symptoms and disease activity biochemically. At age 14, she underwent a laparoscopic ileocecectomy, but pain requiring hospitalizations returned. It was determined that Gianna failed medical and surgical therapy, and the decision was made to start vedolizumab, a newly approved biologic agent directed at adhesion molecules.
Vedolizumab was approved by the Food and Drug Administration in May 2014 for use in patients with moderate to severe ulcerative colitis and Crohn’s disease who have demonstrated a diminished or inadequate response to a TNF blocker or immunomodulator, or who have demonstrated a continued dependence on corticosteroids. Vedolizumab is a monoclonal antibody that binds to integrin α4β7, blocking in a gut-selective way adhesion of T cells and thereby blocking a major pathway of inflammation. Similar to infliximab in administration, patients are given loading doses of the medication, followed by infusions every 8 weeks thereafter. It has been our experience that patients start to see an improvement in symptoms following the fourth infusion, at approximately 3 months into therapy.
Crohn’s disease, ulcerative colitis, and indeterminate colitis affect approximately 1.5 million Americans, and the onset is typically in the second and third decades of life. Increasingly, children under 6 years of age are identified with very early onset inflammatory bowel disease. The causes of IBD are multifactorial, and a genetic risk component has been clearly identified. Newer studies have demonstrated more than 160 gene regions that confer risk for developing IBD. Environmental and immunologic factors also have a clear role in causing the disease. Over the last 2 decades, the incidence rate of Crohn’s disease has nearly doubled. It has been postulated that the Westernized diet coupled with our use of antibiotics and other factors has caused this increased frequency and severity of IBD. More recently, scientists at CHOP and elsewhere have been able to precisely identify the microbiological composition of the gut bacteria, termed the microbiome. There are striking differences in the composition of the early microbiome in urbanized populations. It is felt that these changes may promote proinflammatory activity in the gut, and are possibly related to a number of autoimmune processes.
Treatment for IBD includes a number of different medical strategies, nutritional therapy, and at times surgical therapy. The traditional medical approach was to “step up” from initial therapy with mesalamine, then to prednisone, and then to immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate. With the introduction of the biologic therapies, several different therapy strategies emerged. The initial biologic therapies include infliximab and adalimumab, which are directed against tumor necrosis factor alpha (TNFα). These parenteral therapies are highly effective and, despite the potential side effect profile, are increasingly used as first-line, top-down therapy. These anti- TNFα medications may be used as monotherapy, or in combination with immunosuppressive agents or other conventional forms of therapy. More recently, biologic therapy against adhesion molecules and other strategies have been developed, but are not yet well studied in children and adolescents.
Many patients have profound malnutrition or long-term growth failure at the time of presentation. There has been increasing focus on the role of nutrition in the therapy for all patients with IBD. The administration via nasogastric tube of liquid nutritional formula has been shown to induce a remission in a significant number of Crohn’s disease patients and therefore is commonly employed as a first-line therapy. Typically, the nasogastric (NG) tube is inserted by the family or by the patient each night and removed in the morning, delivering thousands of calories. Some patients rely on this NG nutrition for years. Surgery is also appropriate therapy for some patients. Crohn’s disease can result in strictures and fistulae, and resection of the severely affected area is a typical operation. Unfortunately, Crohn’s disease has a tendency to recur, particularly at the site of the anastomosis. Biologic therapy has been shown to have a significant role in preventing recurrence. Gianna, now 15, is improving on vedolizumab and nasojejunal (NJ) feedings. She has had a couple of hospitalizations to replace her NJ tube, but otherwise continues to be followed as an outpatient in the Center for Pediatric Inflammatory Bowel Diseases at CHOP.
Inflammatory bowel diseases are not currently curable. There are excellent medical and surgical therapies, but the choice of these must be considered based on the severity, extent, type, and location of the disease. The consequences of early therapeutic choices can have a profound effect on the options available years and decades later. The Center for Pediatric Inflammatory Bowel Diseases at CHOP, the largest in the country, cares for approximately 1500 active patients and provides multispecialty care directed at all of the different manifestations and consequences of the disease. There is also a formal transition program to adulthood and care at the Hospital of the University of Pennsylvania, as well as other centers. CHOP’s center also performs extensive basic science, clinical, and translational research to improve the lives of children and adolescents with IBD.
Gianna’s Treatment Progression
Date and treatment:
- 4/08: Mesalamine and metronidazole
- 10/08: 6-mercaptopurine (6MP)
- 10/09: Infliximab, by infusion at 5mg/kg/dose every 8 weeks
- 6/10: Infliximab, by infusion 10 mg/kg/dose every 8 weeks
- 10/10: Infliximab, by infusion 10 mg/kg/dose every 6 weeks
- 3/11: Infliximab, by infusion 10mg/kg/dose every 4 weeks; 6MP 100mg daily
- 4/12: Add methotrexate 25 mg sq., weekly
- 7/14: Laparoscopic ileocecectomy
- 10/14: Exclusive nasojejunal feedings
- 9/14: Vedolizumab, 300 mg IV every 8 weeks
To refer a patient to the IBD Center, call 215-590-3630.