IBD Better Understood, Still a Clinical Challenge

A related video is at www.youtube.com/InternalMedicineNews

FORT LAUDERDALE, FLA. — Despite greater understanding of genetic influences and phenotypic manifestations and the availability of multiple immunomodulatory medications, inflammatory bowel disease continues to pose significant clinical challenges.

“Classically, in inflammatory bowel disease we talk about ulcerative colitis and Crohn's disease, but sometimes there is so much overlap it's hard to tell the difference,” Dr. Sunanda Kane said. For example, although the mucosal disease in ulcerative colitis is generally superficial, if the ulcers are deep, the patient can have more pain than would be expected.

“So we are trying to move away from the black-and-white categories of ulcerative colitis and Crohn's disease and move more toward thinking about the mechanisms of the inflammatory response and the individual patient's phenotype,” said Dr. Kane of the Mayo Clinic, Rochester, Minn.

“We don't fully understand what causes Crohn's and colitis, but we do know that the normal gut is always mildly inflamed. It has to be because this is what 'tastes' the environment and determines what's friend and what's foe,” she said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.

In certain circumstances, such as exposure to bacterial products, the gut can become more acutely inflamed; if the inflammation is not downregulated, it can result in chronic inflammatory bowel disease (IBD).

Genetic studies have begun to reveal genes that predispose a person to an inability to downregulate gut inflammation, such as the NOD2/card15 gene, located at chromosome 16q12. This gene's product is related to immune response to bacteria. Mutations in this gene are associated with Crohn's disease through abnormal activation of downstream inflammatory cell signaling, she explained.

Environmental influences also act as disease modifiers. Diet, smoking, and stress all can contribute to worsening of disease, as can the use of antibiotics—particularly penicillin and the other 'illins'—and NSAIDs, she said.

“There is a 30% increased risk of disease flare with regular NSAID use in IBD, so when patients have extraintestinal manifestations or concomitant rheumatologic conditions … make sure they use drugs other than NSAIDs,” she said.

Treatment also remains challenging, despite the availability of immunomodulating drugs. Infliximab, adalimumab, and certolizumab have been used successfully, but etanercept and onercept have not been superior to placebo, and ulcerative colitis has worsened in patients treated with rituximab for other conditions.

Meanwhile, surgery rates for Crohn's disease have not declined. In a retrospective study of 2,573 patients treated over 25 years in a French center, the cumulative probability of receiving immunosuppressants rose from 0 in 1978 to 0.56 in 2002. But the cumulative risk of intestinal resection within 5 years remained steady, from 0.35 to 0.34 (Gut 2005;54:237-41).

Sometimes luminal inflammation is the least of the patient's problems. “With potential complications including primary sclerosing cholangitis, pyoderma gangrenosum, and anterior uveitis, a little diarrhea isn't always such a big deal,” she said.

Dr. Kane disclosed that she is a consultant for and receives research support from several companies, including Elan Pharmaceuticals Inc., Procter and Gamble, Shire Pharmaceuticals Inc., and UCB Pharma Inc. SDEF and this news organization are owned by Elsevier.

A related video is at www.youtube.com/InternalMedicineNews

FORT LAUDERDALE, FLA. — Despite greater understanding of genetic influences and phenotypic manifestations and the availability of multiple immunomodulatory medications, inflammatory bowel disease continues to pose significant clinical challenges.

“Classically, in inflammatory bowel disease we talk about ulcerative colitis and Crohn's disease, but sometimes there is so much overlap it's hard to tell the difference,” Dr. Sunanda Kane said. For example, although the mucosal disease in ulcerative colitis is generally superficial, if the ulcers are deep, the patient can have more pain than would be expected.

“So we are trying to move away from the black-and-white categories of ulcerative colitis and Crohn's disease and move more toward thinking about the mechanisms of the inflammatory response and the individual patient's phenotype,” said Dr. Kane of the Mayo Clinic, Rochester, Minn.

“We don't fully understand what causes Crohn's and colitis, but we do know that the normal gut is always mildly inflamed. It has to be because this is what 'tastes' the environment and determines what's friend and what's foe,” she said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.

In certain circumstances, such as exposure to bacterial products, the gut can become more acutely inflamed; if the inflammation is not downregulated, it can result in chronic inflammatory bowel disease (IBD).

Genetic studies have begun to reveal genes that predispose a person to an inability to downregulate gut inflammation, such as the NOD2/card15 gene, located at chromosome 16q12. This gene's product is related to immune response to bacteria. Mutations in this gene are associated with Crohn's disease through abnormal activation of downstream inflammatory cell signaling, she explained.

Environmental influences also act as disease modifiers. Diet, smoking, and stress all can contribute to worsening of disease, as can the use of antibiotics—particularly penicillin and the other 'illins'—and NSAIDs, she said.

“There is a 30% increased risk of disease flare with regular NSAID use in IBD, so when patients have extraintestinal manifestations or concomitant rheumatologic conditions … make sure they use drugs other than NSAIDs,” she said.

Treatment also remains challenging, despite the availability of immunomodulating drugs. Infliximab, adalimumab, and certolizumab have been used successfully, but etanercept and onercept have not been superior to placebo, and ulcerative colitis has worsened in patients treated with rituximab for other conditions.

Meanwhile, surgery rates for Crohn's disease have not declined. In a retrospective study of 2,573 patients treated over 25 years in a French center, the cumulative probability of receiving immunosuppressants rose from 0 in 1978 to 0.56 in 2002. But the cumulative risk of intestinal resection within 5 years remained steady, from 0.35 to 0.34 (Gut 2005;54:237-41).

Sometimes luminal inflammation is the least of the patient's problems. “With potential complications including primary sclerosing cholangitis, pyoderma gangrenosum, and anterior uveitis, a little diarrhea isn't always such a big deal,” she said.

Dr. Kane disclosed that she is a consultant for and receives research support from several companies, including Elan Pharmaceuticals Inc., Procter and Gamble, Shire Pharmaceuticals Inc., and UCB Pharma Inc. SDEF and this news organization are owned by Elsevier.

A related video is at www.youtube.com/InternalMedicineNews

FORT LAUDERDALE, FLA. — Despite greater understanding of genetic influences and phenotypic manifestations and the availability of multiple immunomodulatory medications, inflammatory bowel disease continues to pose significant clinical challenges.

“Classically, in inflammatory bowel disease we talk about ulcerative colitis and Crohn's disease, but sometimes there is so much overlap it's hard to tell the difference,” Dr. Sunanda Kane said. For example, although the mucosal disease in ulcerative colitis is generally superficial, if the ulcers are deep, the patient can have more pain than would be expected.

“So we are trying to move away from the black-and-white categories of ulcerative colitis and Crohn's disease and move more toward thinking about the mechanisms of the inflammatory response and the individual patient's phenotype,” said Dr. Kane of the Mayo Clinic, Rochester, Minn.

“We don't fully understand what causes Crohn's and colitis, but we do know that the normal gut is always mildly inflamed. It has to be because this is what 'tastes' the environment and determines what's friend and what's foe,” she said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.

In certain circumstances, such as exposure to bacterial products, the gut can become more acutely inflamed; if the inflammation is not downregulated, it can result in chronic inflammatory bowel disease (IBD).

Genetic studies have begun to reveal genes that predispose a person to an inability to downregulate gut inflammation, such as the NOD2/card15 gene, located at chromosome 16q12. This gene's product is related to immune response to bacteria. Mutations in this gene are associated with Crohn's disease through abnormal activation of downstream inflammatory cell signaling, she explained.

Environmental influences also act as disease modifiers. Diet, smoking, and stress all can contribute to worsening of disease, as can the use of antibiotics—particularly penicillin and the other 'illins'—and NSAIDs, she said.

“There is a 30% increased risk of disease flare with regular NSAID use in IBD, so when patients have extraintestinal manifestations or concomitant rheumatologic conditions … make sure they use drugs other than NSAIDs,” she said.

Treatment also remains challenging, despite the availability of immunomodulating drugs. Infliximab, adalimumab, and certolizumab have been used successfully, but etanercept and onercept have not been superior to placebo, and ulcerative colitis has worsened in patients treated with rituximab for other conditions.

Meanwhile, surgery rates for Crohn's disease have not declined. In a retrospective study of 2,573 patients treated over 25 years in a French center, the cumulative probability of receiving immunosuppressants rose from 0 in 1978 to 0.56 in 2002. But the cumulative risk of intestinal resection within 5 years remained steady, from 0.35 to 0.34 (Gut 2005;54:237-41).

Sometimes luminal inflammation is the least of the patient's problems. “With potential complications including primary sclerosing cholangitis, pyoderma gangrenosum, and anterior uveitis, a little diarrhea isn't always such a big deal,” she said.

Dr. Kane disclosed that she is a consultant for and receives research support from several companies, including Elan Pharmaceuticals Inc., Procter and Gamble, Shire Pharmaceuticals Inc., and UCB Pharma Inc. SDEF and this news organization are owned by Elsevier.