Diagnostic Testing In IBD
In 1997 we reported in Gastroenterology that patients with Crohn’s disease who are being evaluated for disease extent or recurrence could undergo a routine small bowel barium study and get at least as good results as when a small bowel barium study using a nasogastric tube (known as a small bowel enema or small bowel enteroclysis). However, small bowel barium studies can sometimes be insensitive at picking up Crohn’s disease. Hence, we were looking for other imaging techniques to help us evaluate patients with Crohn’s disease.
For a review on imaging tests in IBD see: Mackalski BA, Bernstein CN. New diagnostic imaging tools for inflammatory bowel disease. Gut 2006 May; 55(5):733-41.
Endoscopy remains the main method of diagnosing IBD, particularly if there is colonic involvement (all those with ulcerative colitis and the 50-60% of persons with Crohn’s disease who have colonic disease as well). An important aspect of endoscopy is taking biopsies. The review of the biopsies (snips of tissue) by the pathologist can help distinguish Crohn’s disease from ulcerative colitis some of the time. Biopsies are also important when looking for pre-cancer type changes (dysplasia).
In the past 5 years capsule endoscopy has become an important diagnostic tool that can assess an area of the small bowel, not seen with routine upper or lower endoscopy. Capsule endoscopy entails swallowing a video camera, small enough to be placed within a capsule that can be easily swallowed. The video camera can take 8 hours of images and transmits them to a receiver worn on the patient’s belt. Then the person goes about his/her day and then brings the receiver back to our offices where the information gets downloaded onto a computer and then Dr. Bernstein reads the study off the computer. While capsule endoscopy offers the advantage of visualizing the entire length of the small bowel, it is limited in its ability to accurately determine where in the small bowel an identified lesion is located, and there is no capacity to biopsy a lesion once identified. Another new endoscopic tool is called single balloon or double balloon endoscopy. With the help of a balloon system the endoscope is able to be maneuvered through the curvy small bowel and get all the way to the end. These balloon endoscopy systems have the advantage that one can biopsy lesions that are seen through the scope. However, a disadvantage is that they are tedious and long procedures. Currently, few centres in Canada perform balloon endoscopy (and none in Manitoba).
New Studies 2011-2013
Chisick L, Oleschuk C, Bernstein CN. The utility of TPMT testing in inflammatory bowel disease. Canadian Journal of Gastroenterology 2013; 27: 39-43
Azathioprine and its metabolite, 6-mercaptopurine are commonly used to treat IBD. An important potential side effect is a decrease in white blood cell count. If white blood cell counts drop too low (ie below 3000) there is a significant risk for infection and if it drops very low (below 1000) there is a risk for even life threatening infections. These drugs are metabolized by an enzyme called thiopurine methyl transferase (TPMT). About 10% of the population has low levels of this enzyme and less than 1% have unmeasureable levels of this enzyme. If this enzyme level is low then people using these drugs are at greater risk of having active metabolites of the drug and hence developing low white blood cell counts. In 2008 at the health Sciences Centre, Winnipeg we developed a blood test to measure this enzyme. Now we never prescribe either of these drugs without checking the enzyme level first. If we determine that patients have intermediate levels of the enzyme the goal should be to introduce lower doses of the drug. If the enzyme levels are low or unmeasureable then the drug should not be initiated at all-too risky. If the levels are normal then the drug can be initiated at full dose. This could be helpful in expediting response to the drug since it is slow acting.
In this study by Laura Chisick et al 423 of the IBD patients who underwent TPMT testing from the practices of 11 Manitoba gastroenterologists in 2008—2010 were assessed. 8.3% had intermediate levels and 93.4% had normal levels. Only 1 subject had a low level. Patients with intermediate TPMT levels were generally started at lower doses than patients with normal TPMT levels (1.0 +/- 0.6 mg/kg vs 1.8 +/- 0.5 mg/kg). Of the subjects with normal TPMT levels, only 37.8% were dosed with good starting doses of drug. Each month approximately 5%-10% of subjects developed low white blood cell counts and most had normal TPMT enzyme levels. We concluded that normal TPMT levels did not prevent the development of low white blood cell counts. Further, physicians are not utilizing TPMT levels to substantially dose thiopurines at the outset which may limit the speed at which adequate doses are reached to facilitate remission.
The bottom line for patients is that we have this test available in Manitoba. It is a simple blood test. Before starting thiopurine medication TPMT enzyme levels should be checked first. Even if the level is normal regular blood count monitoring is still advised since low white blood counts can still occur even with normal TPMT enzyme levels. However if TPMT enzyme levels are at an intermediate level then drug dosing should be lower and blood count monitoring more vigilant. If TPMT enzyme levels are low the drug should not be started in most cases.
Sam JJ, Razik R, Bernstein CN, Thanabalan R, Nguyen G. Physicians’ perceptions of risks and practices in venous thromboembolism prophylaxis in inflammatory bowel disease. Digestive Diseases and Science 2013; 58; 46-52.
Fournier MR, Klein J, Minuk GY, Bernstein CN. Changes in liver biochemistry during methotrexate use for inflammatory bowel disease. American Journal of Gastroenterology 2010; 105: 1620-6.
Methotrexate is commonly prescribed to treat Crohn’s disease and we alos use it our Centre to treat ulcerative colitis. One of the potential side effects of methotrexate therapy is to damage the liver so in patients using the drug we check their bloodwork monthly for liver enzyme test abnormalities. In this study we aimed to characterize the spectrum of liver enzyme test (LET) abnormalities that occur while using methotrexate for IBD.
We reviewed the charts of all patients with IBD attending at our clinic who had used methotrexate for IBD (as opposed to who were using it for other diagnoses like arthritis or psoriasis). Note was made of the cumulative methotrexate dose during the peak LET increase, severity of LET increase, and whether normalization occurred. We found 87 persons in our clinic using methotrexate for IBD (67 with Crohn’s disease and 17 with ulcerative colitis and 3 with indeterminate colitis). The average therapy duration was 81 weeks (3-364 week range), and the cumulative average dose was 1813 mg (25-8255 mg range). Thirty-seven (43%) subjects received a cumulative dose of over 1500 mg (we typically prescribe 25 mg doses per week). 67 persons (77%) had normal LETs, and in 51 (76%) LETs remained normal throughout methotrexate therapy. In the 16 (24%) who developed LET abnormalities, 7 (44%) had underlying risk factor(s) for liver disease.
Normalization (without dose reduction) occurred in 14 (88%) while continuing methotrexate.
Of 20 persons with abnormal LETs at baseline, 9 (45%) subsequently normalized while continuing methotrexate, 9 (45%) worsened. 17 liver biopsies were performed in 11 persons and were classified as minimal to no change in 15 (88%). Advanced changes were never seen.
We concluded that Methotrexate is commonly associated with LET abnormalities but these frequently normalize while patients are still on therapy and in only 5% will drug discontinuation be necessary. Liver biopsies rarely have substantive abnormalities. Hence this study has changed our practice and we are no longer doing routine liver bipsies on patients after long term use of methotrexat. We are offering them to patients who have persistent LET abnormalities.
Colonoscopy complication rate study
Singh H, Proulx S, Kaita L, Bernstein CN, Moffatt M. Colonoscopy and its complications across a Canadian regional health authority. Gastrointestinal Endoscopy 2009; 69: 665-71.
This was a community based study assessing the complication rate from colonoscopy in the Winnipeg Regional Health Authority over a two year period. We found a higher complication rate if the index colonoscopy was performed by endoscopists, who performed the lowest volume of colonoscopies.
Another diagnostic frontier is the pursuit of blood tests (measuring antibodies) that could predict whether IBD is present in patients with gastrointestinal symptoms or that could distinguish between Crohn’s disease and ulcerative colitis. There is no single blood test that suggests that Crohn’s disease is present with a very high degree of certainty, however an antibody test called ASCA is very suggestive of Crohn’s disease when it is positive.
Getting IBD Patients the Information They Want and/or Need
Bernstein KI, Promislow S, Walker JR, Bernstein CN. The information needs and preferences of recently diagnosed patients with IBD. Inflammatory Bowel Diseases 2011; 17: 590-98.
The aim of this study was to assess the information needs and experiences of patients who were recently diagnosed with IBD. 74 patients, diagnosed with Crohn’s disease or ulcerative colitis, 3-24 months previously were recruited from gastroenterology clinics and completed the information needs survey.
The most frequent sources of information in the first 2 months after diagnosis were the gastroenterologist and the Internet. 24% of patients reported feeling dissatisfied with the information they were given at the time of their diagnosis, 31% were moderately satisfied, and 45% were very satisfied. When specific topics were considered however, there were many areas of information about the disease, its treatment, and self management that patients considered to be important, but about which they received little or no information about. When patients were asked to consider how they would prefer to receive information if they were considering a new treatment in the future, 68% indicated that they preferred information from a medical specialist.
We concluded that given the large number of topics judged to be important and the complexity of the information required, it would be very difficult to communicate this information in oral discussion during typical consultation visits. Hence supplementing physician-patient consultations with well-designed written information or a website recommendation may produce more effective communication and education.
Promislow S, Walker JR, Taheri M, Bernstein CN. How well does the Web answer patients’ questions about IBD. Canadian Journal of Gastroenterology 2010; 24L 671-7.
• The Internet is increasingly important as a source of health information. Our aim was to assess how well common websites answered patients’ questions about IBD. 30 websites were identified and evaluated. Based on a previous survey of patient information needs, we developed a comprehensive list of questions in three areas: medical information (7 items), medical treatment (6 items), and self-management (8 items). The websites were evaluated for the amount of information they provided to answer each question and with two standard measures of information quality: the DISCERN and EQIP scales. We found that the 4 particularly strong websites, scoring highest in terms of IBD information, were the Crohn’s and Colitis Foundation of America (CCFA, mean information score 4.3 out of 5), About.com (4.2), HealthCentral (3.8), and WebMD (3.8). These websites also scored well on the DISCERN and EQIP quality scales. Most websites provided at least adequate information on common symptoms, complications, treatments, and what is known (or not known) about the causes of IBD but many did not provide adequate information about prognosis, possible side effects of treatment, and risk of developing cancer. Information concerning self-management was covered to a very limited extent. We concluded that Websites could be strengthened by providing more of the information patients judge to be important and by more clearly identifying sources of information and the date information was updated. Most sites would benefit from more attention to reducing reading level and improving organization of material.
WORLD DIGESTIVE HEALTH DAY-IBD MAY 29, 2010
The following will appear in an upcoming edition of the Journal of Clinical Gastroenterology. For 2010 Dr. Charles Bernstein is the Chairman of the WDHD campaign of awareness of IBD
Each year on May 29 the World Gastroenterology Organization (WGO) holds a World Digestive Health Day (WDHD) to raise awareness about a particular disease. The disease for 2010 has been Inflammatory Bowel Disease; a disease that affects millions. The public health campaign which involves WGO’s 110 national societies and 50,000-plus physicians is promoted throughout the world. WGO together with its Foundation compiles a list of resources, tools, and most importantly a corresponding Global Guideline. This year’s IBD guideline, offered in English, Portuguese, Mandarin, French, Russian and Spanish, provided clinical cascades for treatment at different resource levels. Other tools included tips for living with IBD, frequently asked questions on IBD by patients, important issues for physicians managing patients with IBD and other material in e-WGN, WGO’s e-newsletter. As, Chair of the 2010 WDHD campaign, Dr. Bernstein worked to create these tools with the help of other IBD experts
Digestive Disease Week (DDW), an annual event in the U.S. included events focusing on both WDHD and IBD. An IBD Task Force was created and experts from all over the world presented on the disease from the view of their specific country. The epidemiology, phenotype presentations, diagnostics, therapeutics and important differential diagnosis considerations were discussed. Planning was initiated for a Symposium to be held 24 October, 2010 at the United European Gastroenterology Week in Barcelona where international renown IBD investigators presented on nutritional issues in IBD, diagnostic testing in IBD and choosing between surgery and biological therapy in IBD.
Over 25 member societies took part in World Digestive Health Day by hosting events throughout the year with over 50 events taking place. Various events focusing on IBD included public campaigns, courses and lectures on treatments of IBD, marathons, national meetings, press conferences, creating a country’s own IBD Day or celebrating World Digestive Health Day, publications and much more. Here are some highlights from events that took place all over the world.
The Argentine Society of Gastroenterology held a press conference to increase media awareness, bringing in experts from Spain, the United States of America and Argentina to assess IBD diagnosis, management and treatment, held multiple courses offering new information on IBD and created a public awareness campaign which was promoted on their website.
In India, experts successfully promoted IBD awareness in rural areas by offering both information and discounts on procedures such as colonoscopies throughout the month of May. The second national IBD meeting under the auspices of the Colitis and Crohns Foundation (India) took place on May 23, 2010. This year, the Secretaries of all three major Gastroenterology societies of India held a program which included a ceremonial Meeting, An IBD Symposium, and Release of IBD Patient awareness literature in Indian languages.
Under the patronage of the Ministry of Health in Syria, the Syrian Group for the Study of Inflammatory Bowel Disease (IBD), in collaboration with the Syrian Society of Gastroenterology, organized a WDHD event that highlighted IBD with the aim to raise awareness about the disease.
In Guatemala, a gala event to open the IBD awareness meeting was held, along with multiple newspaper publishing’s to raise IBD awareness among the general public. The involvement of WGO’s member societies is what has made World Digestive Health Day 2010 a success.
Two important publications have arisen as part of this campaign. They include:
Bernstein CN Fried M, Krabshuis JH, Cohen H, Eliakim R, Fedail S, Gearry R, Goh KL, Hamid S, Khan AG, LeMair AW, Malfertheiner, Ouyang Q, Rey JF, Sood A, Steinwurz F, Thomsen OO, Thomson A, Watermeyer G.. World Gastroenterology Organization Practice Guidelines for the Diagnosis and Management of IBD in 2010. Inflammatory Bowel Diseases 2010; 16(1): 112-24.
While IBD have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.
Baumgart DC, Bernstein CN, Abbas Z, Colombel JF, Day AS, D’Haens G, Dotan I, Goh KL, Hibi T, Kozarek RA, Quigley EM, Reinisch W, Sands BE, Sollano JD, Steinhart AH, Steinwurz F, Vatn MH, Yamamoto-Furusho JK. IBD Around the world: Comparing the epidemiology, diagnosis, and treatment: Proceedings of the World Digestive Health Day 2010 – Inflammatory bowel disease task force meeting. Inflammatory Bowel Diseases 2011; 17: 639-44.
Upon the occasion of WDHD 2010 a WGO IBD task force was compiled from leading international specialists and researchers. The task force also included members of the American Gastroenterological Association (AGA), International Organization for the Study of Inflammatory Diseases (IOIBD) and the European Crohn’s and Colitis Organization (ECCO) of the United European Gastroenterology Federation (UEGF). The goal of the task force was to bring together IBD specialists from around the world to discuss the epidemiology, diagnosis, and management of IBD within different regions. This is a summary of the WGO task force meeting at the American Gastroenterological Association’s (AGA) Digestive Disease Week, held in New Orleans, Louisiana, USA, May, 2010. The expert panel identified the most pressing issues in IBD worldwide: reliable epidemiological data, global collaboration in clinical and basic research, the approach to distinguishing intestinal tuberculosis from Crohn’s disease, access to specialist care and access to the latest diagnostic and therapeutic strategies. The meeting was chaired by Dr. Charles Bernstein. This publication was a summary of that meeting.