Pathologist Explores Role
A UConn pathologist may be a step closer to identifying the cause of Crohn’s disease, a severe, chronic inflammatory bowel disease that affects some 500,000 people in the United States.
In a new study, Dr. Herbert Van Kruiningen, professor and head of the pathobiology and veterinary science department, reports environmental findings in families with multiple cases of Crohn’s disease. He conducted the research in northern Belgium, where he says there is “an inordinate frequency” of the disease – as many as five cases per family. Symptoms of the disease include chronic diarrhea, fever, weight loss, fatigue, abdominal cramps, joint pain, and skin lesions.
While much research on Crohn’s disease has focused on genetic susceptibility, only a handful of scientists have examined environmental factors.
Van Kruiningen studied 21 Belgian families that had multiple cases per family. He also studied 10 control families who did not have the disease. Each family member completed a 176-item questionnaire, and provided mouth cultures, blood, and stool samples.
Finding families for the control group was challenging, he says:“Families with the disease were eager to participate in the study. They’re worried. They want answers. But finding large-size, healthy families willing to meet together and fill out a questionnaire with more than 170 items wasn’t easy.”
The questionnaires addressed two different time frames. One group of questions covered family history from childhood to age 20, including environment, water and food consumption, travel, pets, and social activities. The other questions addressed a time frame of 10 years before the onset of disease within a household. “We need to look back, because many people deny they’re ill and postpone seeing a doctor,” says Van Kruiningen. “They’ll see their local practitioner and he might treat them, but they will ultimately find themselves in the hands of a gastroenterologist. There’s a delay before someone says ‘you’ve got Crohn’s disease’.”
Van Kruiningen says he developed a rapport with the families. “They were pleased we were there,” he says. “We would sit at the dining room table in their homes, and go through question by question in Dutch. A Belgian nurse was the translator. We were a good team. After a while I came to know where questions were going to arise that required explanation.”
During the interviews, Van Kruiningen discovered conditions that surprised him.
“Much of the literature indicates that Crohn’s disease occurs more frequently in urban populations,” he says. “I was surprised to find that of the villages we visited, nine out of 10 were located in agricultural communities. And the tilled land came right up to the edge of the houses. I was also struck by the fact that a good number of these Belgian families used human waste on their vegetable gardens. Also, many families ate a table spread made of uncooked pork.”
Robert Vlietinck, an internationally known geneticist and biostatistician from the Katholieke Universiteit of Leuven, Belgium, helped analyze the data, working at the Storrs campus on three separate occasions.
“Once the statistics were done, we found that families with Crohn’s disease drank well water during their formative years,” Van Kruiningen says, “whereas families in the control group did not. The drinking of well water is a risk factor, but I don’t know why. It could be that a virus or bacterium occurs in the water, or this might be an incidental association.”
He also found that families with multiple cases of Crohn’s disease had a greater frequency of hand, foot, and mouth disease and of hepatitis A, than the families in the control group. “This suggests that families that acquired Crohn’s disease had more exposure to enteroviruses,” Van Kruiningen says. “These viruses are acquired by fecal contamination of water or uncooked foods.”
Another finding was that those in the control group often had a cat in the house, but families with Crohn’s disease did not. “People who have cats hug and kiss them and sleep with them,” he says. “Cats sometimes walk on food preparation surfaces. It’s not absurd to suggest that close contact with a cat may have a protective role.
“We’ve made some associations,” Van Kruiningen says, “and they warrant further study.”
The research has been published in the April issue of the medical journal Inflammatory Bowel Diseases.