RxPG News : Crohn's Disease

Crohn's disease or gastrointestinal endometriosis?

Fri, 22 Feb 2008 08:02:46 PST

( from http://www.rxpgnews.com ) Endometriosis is a condition of unknown etiology in which endometrial tissue occurs at extra-uterine sites, including ovaries, fallopian tubes, and gastrointestinal tract. It usually occurs between 30 and 40 years of age. Four to 17% of menstruating women develop endometriosis. When the disease involves the small bowel, it usually has a benign course, but in rare circumstances, it may present as abdominal emergency. Invasive bowel endometriosis can present as bowel obstruction. The major cause of obstruction is stricture formation and adhesions, which occasionally mimic Crohn's disease or a malignancy in its clinical presentation.

Gastrointestinal endometriosis is suggested by dysmenorrhea, menorrhagia or perimenstrual symptoms. Frank intestinal symptoms are usually associated with intestinal obstruction. While intestinal symptoms may occur during or be exacerbated by the menses, this association may not always be present. The symptoms coincide with menstruation in only 18-40% of the cases. A recurring crampy lower or mid-abdominal pain is the most common presenting symptom for both intestinal endometriosis and Crohn's disease. Other symptoms which may occur in both entities include diarrhea, constipation, nausea, vomiting, fever, anorexia, and weight loss.

A case report published on January 7, 2008 in the World Journal of Gastroenterology describes a desperate patient who presented to Dr. Zafer Teke of Pamukkale University Hospital, Turkey, in 2006. This patient was quite a challenge for Dr. Teke. She was 31 years old with perimenstrual lower and mid-abdominal pain irradiating to the back, and lower abdominal fullness for 3 years, at first monthly, but later continuous, and gradually increasing in severity. She gave a history of moderate dysmenorrhea and menorrhagia, but no dyspareunia. Her only medication was an oral contraceptive. She had delivered a healthy baby.

Her gynecologist at a women's health clinic had diagnosed her with small bowel endometriosis, based on interviews and her clinical course. As only oral contraceptive therapy was started, the symptoms due to partial mechanical bowel obstruction had gradually improved. The lack of response to oral contraceptive therapy had encouraged her gynecologist to perform an exploratory laparotomy. The gynecologist was only able to perform a biopsy from the highly inflamed areas. Biopsy results were non-specific inflammation. The patient was then referred to Dr. Teke's institution to identify the underlying pathology.

In an effort to improve the condition of the patient, Dr. Teke initially decided to treat the patient with conservative measures, and the patient responded to this treatment. However, after ingesting a small amount of food she again complained of abdominal pain, and plain abdominal radiography once more showed mechanical bowel obstruction. After improvement with conservative management and obtaining adequate informed consent, the patient was operated on by Dr. Teke. The operative appearance was thought to indicate Crohn's disease, but in view of the close relationship of the ovaries, tubes and uterus, an immediate gynecological opinion was obtained. The on-call gynecology registrar did not consider the appearance to be due to primary gynecological pathology. An approximately 40 cm segment of distal small bowel had four strictures and three internal fistulas. Histopathological examination of the resected specimen was consistent with Crohn's disease. The surgical treatment led to rapid resolution of the symptoms.

The differential diagnosis of Crohn's disease with intestinal endometriosis may be difficult pre-operatively. Dr. Teke noted that even lower gastrointestinal flexible endoscopy may show no findings suggestive of Crohn's disease, as in his patient. Indeed, there may be a similarity between the two entities in terms of clinical presentation, symptomatology, radiological appearances, surgical and pathological findings. Due to a relatively high percentage of endometriosis among the female population of child-bearing age globally, and the unavailability of a precise test differentiating Crohn's disease from bowel endometriosis, this case reported by Dr. Teke is surely worth the attention of both doctors and women at large.

Alternative strategy better for Crohn's Disease

Fri, 22 Feb 2008 06:52:36 PST

( from http://www.rxpgnews.com ) An international research study, published in The Lancet, has thrown into question the current method of treating Crohn’s disease – opening the door to a safer and more effective treatment option for sufferers of the chronic disease.

“Our study clearly demonstrated that this alternative treatment method was more effective at inducing disease remission than the conventional method,” said Dr. Brian Feagan, Director of Robarts Clinical Trials at Robarts Research Institute at The University of Western Ontario. Dr. Feagan coordinated the research trial and is an author on the study. “Not only were patients more likely to get their disease under control, but they were also spared exposure to steroids – the extended use of which is linked with metabolic disease and even increased mortality. It’s simply a safer, more effective treatment method.”

Called a "step-up" approach, the conventional treatment for Crohn’s disease involves first administering steroids in order to control the patient’s symptoms (abdominal pain and bloody diarrhea); the next step involves administering immune-suppressing drugs, which prepare the body to receive the third medication – an antibody that curbs the inflammatory response at the root of the disease.

The alternative strategy, called "top-down" therapy, employs early use of immune-suppressing drugs combined with an antibody in order to address the disease from the start. Symptom-treating steroids may never even be needed.

The two-year study was conducted at research centres in Belgium, Holland, and Germany and involved 129 subjects with active Crohn’s disease. 64 patients received the conventional step-up treatment and 65 the combined immune-suppressing method (top-down). 60% of the top-down subjects were symptom-free by the 26th week of the study, compared to only 36% of the step-up subjects.

“This study is a milestone in the management of Crohn’s disease,” said lead author Dr. Geert D’Haens, of the Imelda GI Clinical Research Centre at the Imelda Hospital in Bonheiden, Belgium. “It does not look at the effects of single drug intervention but at strategies to alter the natural history of this chronic destructive condition. All ‘classic’ paradigms for the management of Crohn’s disease need to be questioned.”

The impact of the study goes beyond Crohn’s disease. “We’ve seen similar results in top-down, step-up studies of rheumatoid arthritis,” said Dr. Feagan, “suggesting that the top-down approach could be the best treatment method for other chronic auto-immune diseases such as ulcerative colitis.”

Adalimumab is an effective treatment for refractory Crohn's disease

Tue, 01 May 2007 11:26:31 PST

( from http://www.rxpgnews.com ) A study led by Mayo Clinic found that adalimumab (HUMIRA®)) is an effective treatment for adults with Crohn's disease who do not respond to infliximab (REMICADE®) therapy. These findings were published online today by Annals of Internal Medicine.

Crohn's disease is an inflammatory disorder of the gastrointestinal tract that affects an estimated 500,000 people in the United States. Symptoms include abdominal pain, fever, nausea, vomiting, weight loss and diarrhea. Crohn's disease has no known medical cure. One common therapy is a series of intravenous infusions of infliximab, which blocks tumor necrosis factor, an important cause of inflammation in Crohn's disease.

"Approximately 50 percent of Crohn's disease patients who receive repeated administration of infliximab will eventually develop an allergic reaction, need higher doses, or completely stop responding to the therapy," says William J. Sandborn, M.D., the lead author and a gastroenterologist at Mayo Clinic. "Our goal with this study was to determine if adalimumab was a safe and effective alternative for these patients."

Like infliximab, adalimumab is a human monoclonal antibody that blocks tumor necrosis factor. However, it is administered via a series of subcutaneous injections, rather than intravenously.

The study included 325 patients at 52 sites with moderate to severe Crohn's disease who continued to have symptoms despite infliximab therapy or who could not take infliximab due to an allergic reaction. Researchers found that 21 percent of patients who received adalimumab achieved remission after four weeks, while just 7 percent of patients who received a placebo achieved remission in the same period. Fifty-two percent of patients who received adalimumab achieved an improvement in their clinical symptoms as compared with 34 percent of patients who received a placebo.

"This study demonstrates that in the short term, adalimumab can be safely administered to Crohn's disease patients who are intolerant of infliximab," says Dr. Sandborn. "For those patients, this new therapy is a second chance at remission and a significant improvement in quality of life."

Patients in this study were recruited from tertiary care centers, academic medical institutions and independent research organizations in the United States, Canada and Europe.

Each year, physicians at Mayo Clinic's campuses in Arizona, Florida and Minnesota treat approximately 2,000 patients who have Crohn's disease. For more information on the treatment of Crohn's disease at Mayo Clinic, visit www.mayoclinic.org/crohns/.

This research was funded by Abbott Laboratories. Mayo Clinic receives consulting fees from Abbott Laboratories and Centocor, Inc. for work performed by Dr. Sandborn. Humira (adalimumab) is a product of Abbott Laboratories. Remicade (infliximab) is a product of Centocor, Inc.
http://www.mayoclinic.org/news2007-rst/4047.html?src=email-release