Medical Inspection – Health Blog

Complementary and alternative medicine use by patients with inflammatory bowel disease: An Internet survey

Complementary and alternative medicine (CAM) use is increasing in Western countries. Astin re­ported that 40% of American adults had used some form of CAM in the previous year. CAM differs from conven­tional medicine in many important ways, including beliefs about disease causation, treatment and the nature of the therapeutic relationship between the practitioner and the patient. For example, the patient often plays a much more active role in CAM rather than being a passive re­cipient of therapy as often occurs in conventional medi­cine. Patients often seek CAM after conventional medicine has failed. However, patients may also use CAM because their attitudes and beliefs are more in keep­ing with those of CAM rather than conventional medicine.

The use of CAM by patients with inflammatory bowel disease (IBD) has been the focus of several studies. Smart et al reported in 1986 that only 4% of patients with Crohn’s disease attending an out-patient clinic in The United Kingdom were currently using alternative medi­cine. Verhoef and Sutherland showed that the propor­tion of IBD patients consulting a complementary practitioner for the same reason as they saw their gastroen- terologist (15%) was higher than the proportion (8%) for other gastrointestinal patients. In 1996, Moser et al found that 34% of Austrian IBD patients used alternative therapies. In a recent study, we found that CAM had been used in the previous two years by 51% of patients at­tending clinics of university-affiliated gastroenterologists in Calgary, Alberta. Current use was reported by 33%. The most common reasons for using CAM were the side effects and lack of beneficial effect of conventional treat­ments.

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The most striking finding in this study was the overall, about three to one, preponderance of patients with ulcerative coli­tis versus Crohn’s disease. This is consistent with observa­tions for South Asian immigrants in the United Kingdom.  In the latter report, adults from two hospitals (East Bir­mingham Hospital, the Bradford Royal Infirmary) and chil­dren (St Bartholomew’s Hospital) had a similar diagnosis ratio (three to one) for ulcerative colitis versus Crohn’s dis­ease. This was also observed in an epidemiological evaluation of South Asians residing in Leicestershire, United Kingdom, where 134 South Asians with ulcerative colitis and 31 with Crohn’s disease were seen. The present study also ex­tended these findings to individual subgroups of Indo-Cana- dians, including those born in Canada as well as different migrant groups. Interestingly, this increased ratio of ulcer- ative colitis to Crohn’s disease was not observed in a sequen­tially evaluated non-Indian patient group with IBD from our hospital. Although these studies have not evaluated all Indo-Canadians with IBD in Vancouver and only involved a cohort from a single referral practice, the present findings suggest that patients of South Asian descent in Canada are at greater risk for the development of ulcerative colitis than of Crohn’s disease. These findings are consistent with the view that both diseases arise in individuals with a genetic predis­position but apparently only after exposure to some, as yet unknown, environmental factor.

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Treatment and complications: Medications included 5- aminosalicylates, steroids and immunosuppressants as well as antimicrobial agents. In most patients, more than one medi­cation was administered during the course of their treatment, particularly for Crohn’s disease. For both groups, most were treated with corticosteroids and/or immunosuppressants dur­ing a mean follow-up period of five to six years. Some differ­ences were also evident. The proportion of patients who received only a 5-aminosalicylate (37%) was greater in the ulcerative colitis group than in the Crohn’s disease group (18%), while use of metronidazole was more frequent in pa­tients with Crohn’s disease (45%) than in those with ulcer­ative colitis (11%). More Indo-Canadians with Crohn’s dis­ease required parenteral nutrition during their disease course than those with ulcerative colitis, and a greater proportion of patients with Crohn’s disease required surgical treatment (32%). Only six patients (about 10%) with a diagnosis of ul­cerative colitis required colectomy; of these, five had a pelvic pouch reconstructive procedure. To date, 60% of these pa­tients have developed pouchitis. Finally, two patients with ulcerative colitis had colonic neoplasms detected; both were tubular adenomas and both were endoscopically resected. So far, no other dysplastic lesions or colon cancer has been de­tected in these 84 patients.

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Patient population: In this prospectively studied population cohort of Indo-Canadians residing in the metropolitan area of Vancouver, a clinical diagnosis of ulcerative colitis was es­tablished in 62 of 84 patients (almost 75%) with IBD; the other 22 patients had Crohn’s disease (Table 1). This distri­bution contrasts with the results of a prospectively studied population of 500 patients that included 247 patients with ulcerative colitis and 253 with Crohn’s disease, as well as with studies of the Chinese population of Vancouver with ei­ther ulcerative colitis or Crohn’s disease. This dis­ease-based predominance of ulcerative colitis versus Crohn’s disease was present in the patients born in Canada as well as in migrants to Canada from other countries, including India (Table 2).

For patients with either Crohn’s disease or ulcerative coli­tis, the percentages born in Canada (36% versus 34%, re­spectively) appeared to be similar. All migrants from other countries developed IBD after residing in Canada. The dura­tion of residence in Canada before diagnosis was shorter for patients with Crohn’s disease (mean 8.9 years, range two to 25) than for those with ulcerative colitis (mean 13.5 years, range three to 28).

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Laboratory studies: For each patient, all blood samples were collected into vacutainer glass tubes (Becton Dickinson, Franklin, New Jersey) by a laboratory technologist without knowledge of the patient’s clinical history, investigation re­sults or diagnosis. Blood was also obtained for hematological studies (hemoglobin, white blood cell count and platelet count), erythrocyte sedimentation rate, antinuclear antibod­ies, liver chemistry tests (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase), serum iron studies and serum protein tests, including serum albumin.

Finally, blood samples were collected into vacutainer glass tubes, allowed to clot at room temperature and used for detection of ANCA via two methods: ANCA immuno­fluorescence and ELISA. Serological studies for ANCA were done by a single laboratory technologist blinded to the clini­cal details and diagnosis. If ANCA immunofluoresence was positive, ANCA ELISA was done for autoantibodies to myeloperoxidase (MPO) and serine protease-3 (PR-3). ANCA immunofluorescence: Indirect immunofluorescence for c-ANCA, p-ANCA and atypical p-ANCA was detected with a standardized fluorescent antibody detection method, using a proprietary kit purchased from a commercial supplier (Inova Diagnostics Inc, San Diego, California). Slides were supplied with an adherent layer of cultured hu­man neutrophils. The culture conditions were designed to ensure stability and strong expression of the primary cyto- plasmic granules. The adherent neutrophils were fixed by the manufacturer with either ethanol or formalin. The primary screen for c-ANCA or p-ANCA involved incubation of serum at a one to 20 dilution in phosphate-buffered saline with ethanol-fixed slides for 25 mins at room temperature fol­lowed by a 5 min wash with phosphate-buffered saline. This was followed by another 25 min incubation using affinity-pu­rified antihuman immunoglobulin (Ig) G with a fluorescent tag and a further 5 min wash with phosphate-buffered saline. Coverslips were then applied to the slides, and these were ex­amined with a fluorescence microscope at x500 magnifica­tion.

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Patient groups: Each patient had an established diagnosis of idiopathic ulcerative colitis or Crohn’s disease in the small and/or large intestine based on clinical, radiological, endo- scopic and histological criteria, and negative microbiological studies. Ulcerative colitis was diagnosed when a diffuse inflammatory process involving the rectum and extending proximally within the colon was present. As in previously re­ported studies, disease extent and site were classified as ‘distal disease’ if inflammatory changes were localized in the distal 60 cm based on colonoscopic visualization as well as endoscopic mucosal biopsy, or as ‘extensive disease’ if inflam­matory changes were over 60 cm. Crohn’s disease was diag­nosed from colonoscopic and histological studies showing a segmental or patchy inflammatory process within the colorectum, distal small intestine or both, often with gran- ulomatous changes. In addition, the upper gastrointestinal tract was evaluated with the use of radiological, endoscopic and histological studies. Surgical material, if available, was also examined. During the course of this study, no other form of idiopathic IBD was observed, including the microscopic forms of colitis (lymphocytic or collagenous colitis).

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Previous studies have demonstrated that some anti­neutrophil cytoplasmic autoantibodies (ANCA) may be detected in patients with inflammatory bowel disorders, par­ticularly in those with ulcerative colitis. Recently, in a prospective study of 500 Canadian patients with inflamma­tory bowel disease (IBD) who were evaluated at the Univer­sity of British Columbia, 38.8% were positive for ANCA – 66.3% with ulcerative colitis and 11.9% with Crohn’s dis­ease. In addition, this seromarker persisted in patients with ulcerative colitis, even after proctocolectomy. Oc­casionally, this seromarker may be detected with other forms of IBD, specifically microscopic forms of colitis, including collagenous or lymphocytic colitis, with or without celiac disease. Although a specific subclass, the atypical peri­nuclear ANCA (p-ANCA), are often present if there is co­lonic disease, occasionally patients with Crohn’s disease localized only to the small bowel may also be positive. In a more recent study, the presence of a relatively unique sub­class, the so-called cytoplasmic ANCA (c-ANCA) typically reported in Wegener’s granulomatosis, was observed in a group of 18 patients with extensive colitis. This subclass was not common, occurring in an estimated 2% of patients with IBD at this centre. Interestingly, significant numbers of patients with c-ANCA (ie, almost half) were Indo-Canadians.

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