Inflammatory Bowel Disease an "Equal Opportunity" Condition

Old beliefs that the incidence of inflammatory bowel disease (IBD) in the US is higher among upper class and urban children have been dispelled by an in-depth look at new cases in Wisconsin. The research project has also provided current data to be used in furthering advances in treatment at several levels.

In a study published in the October, 2003 Journal of Pediatrics, researchers from the Medical College of Wisconsin reported that IBD is an "equal opportunity condition" that afflicts comparable percentages of children in cities and rural areas and that incidence is constant regardless of income level, race or ethnicity.

"In IBD, the large intestine and the small intestine get sores and ulcers," said study co-author Subra Kugathasan, MD, Medical College Associate Professor of Pediatric Gastroenterology. "In a slow process that may take years, eventually the ulcers start to bleed, causing blood loss, thickening of the intestine and ultimately malabsorption. It's a destructive disease."

Ulcerative colitis and Crohn's disease are the two major conditions covered by the term inflammatory bowel disease. Both can have a severe and debilitating impact on gastrointestinal function for the life of the patient. "The end result, how the tissue reacts inside, is pretty much the same with both ulcerative colitis and Crohn's disease," said Dr. Kugathasan, "so it's sometimes very difficult to differentiate between them. But they're completely different diseases."

Relatively scattered data accumulated by investigators over the years had led to conclusions that IBD was more common in developed Western nations, with a higher incidence among Caucasians, Jews and people living in urban areas, Dr. Kugathasan noted. Now, he said, recent research indicates that IBD incidence rates are increasing worldwide. IBD is on the rise in Latin America, where it was once thought to be rare, and in far-Eastern countries such as Japan, South Korea and Singapore.

Important Findings in Wisconsin
The study of Wisconsin children with IBD concluded that pediatric IBD crosses many lines. Along with the finding that race, ethnicity, and urban vs. rural environmental factors appear to be irrelevant to IBD incidence in the state; the report said that 90% of the newly diagnosed children had no family history of the disease.

"Conventionally and historically, data suggested that Crohn's disease is a disease of the affluent, a 'Caucasian disease' and maybe a 'Jewish disease,'" said Dr. Kugathasan. "What we found in our study here is that it doesn't matter if you are Jewish or non-Jewish, whether you are Black or White or Hispanic or Asian, whether you live in an urban area or a rural area.

"IBD is equally affecting everybody. That's what I think is the most important thing we've found, suggesting that perhaps the specific environment, and where in the world we are in terms of exposure, plays a greater role than had been believed."

Genetics and environment are commonly accepted as the causes of IBD, a classic example of "nurture" and "nature." In an article they co-authored for the Crohn's and Colitis Foundation of America (CFFA) publication Focus, Medical College student Nicole Collins and Dr. Kugathasan wrote: "Most researchers believe that something in the environment triggers something in people whose genes have made them susceptible to IBD. Once inflammation begins, genes play a large role in maintaining (or not maintaining) the inflammatory reaction."

Dr. Kugathasan said that the most common presentations of IBD in children include rectal bleeding, weight loss, growth failure, chronic diarrhea and abdominal pain.

Varied Treatments and Genetics
Corticosteroids have been used for about 40 years to treat IBD. Children can experience especially severe side effects from steroids, including thinning of the bones and retarded growth, especially when steroids are used in the long term. Newer steroids with power but fewer side effects have been recently approved for use in adults. In the Focus article, Collins and Dr. Kugathasan encouraged parents to discuss what to expect from steroids if they are being considered to help treat IBD in their children.

Long-term therapy for children with ulcerative colitis and Crohn's disease commonly includes the use of the drugs 6-mercaptopurine and azathioprine. These drugs are considered safe and effective. The Focus article points to a recent study showing that starting 6-mercaptopurine at the time of diagnosis can keep children with Crohn's disease in remission for prolonged periods and significantly reduce their need for steroids.

Antibiotics and other common drugs, probiotics and medical procedures such as stem cell transplants are also employed to treat IBD and its symptoms.

In addition, biologic therapy for IBD is starting to come into play. One of the cytokines, a group of chemicals thought to be part of the process that causes intestinal inflammation in Crohn's disease, is being fought with a laboratory-developed antibody now being used with children "off label" pending further study and approval for this specific use. An "adhesion molecule" currently being tested in children may help keep inflammatory immune cells from getting to the colon through the bloodstream and causing colitis.

The first gene associated with Crohn's disease (gene NOD2) has been identified, and Dr. Kugathasan is studying its effect in the IBD children included in the Wisconsin study. With the "fresh" database from a well-defined geographic area provided by the study, Dr. Kugathasan said, genetic research can proceed hand-in-hand with a closer look at the natural history of ulcerative colitis and Crohn's disease.

Tricky Diagnosis in a Large Population
"Any specialist can end up seeing IBD," said Dr. Kugathasan. "In fact, we have cases where children have been sent to psychiatrists and diagnosed with eating disorders and subsequently we diagnosed Crohn's disease. Children with strange skin manifestations of IBD can be seen by dermatologists before they are sent to us. Or they come out of this with severe growth failure and told they need growth hormone treatment before it is discovered to be IBD."

Increased awareness among pediatricians is helping to produce accurate diagnosis of IBD in children more quickly, resulting in earlier intervention, Dr. Kugathasan says, and the delay from presentation to diagnosis has been cut in recent years from an average of 18 months to nine.

"IBD is a disease of adolescents and young adults," said Dr. Kugathasan. "The peak age for diagnosis is anywhere from 15 years to 25 years. Then it tapers right away. We certainly diagnosis children as young as one or two years old, but that's rare. In our study of just children under age 18, more than 20% were under ten years old. Eighty percent were between 11 and 17."

Some estimates place the number of people with IBD in the US at about one million, with 200,000 of them under the age of 18, although Dr. Kugathasan said that those figures are "probably an overestimate." Data from the Medical College study is also playing a role in developing an accurate count of those under age 18 with IBD.

"What we know is incidence data," said Dr. Kugathasan. "We're working with an epidemiologist right now to calculate prevalence data for Wisconsin. Based on our incident data from this report, if you can extrapolate that data to the entire country, right now we're coming down to about 40,000 children in this country affected by the condition, which is a pretty high number to have this chronic, debilitating disease."

Dan Ullrich
HealthLink Contributing Writer

For more information on this topic, see the HealthLink articles New Biologic Therapy Helps Children with Crohn's Disease and The Facts about Ulcerative Colitis.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.