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Complementary medicine use in children and young adults with inflammatory bowel disease
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2002 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 97, No. 2, 2002 ISSN 0002-9270/02/$22.00 PII S0002-9270(01)04036-9
Complementary Medicine Use in Children and Young Adults With Inflammatory Bowel Disease Robert Heuschkel, M.B.B.S., M.R.C.P.C.H., Nadeem Afzal, M.B.B.S., M.R.C.P., Anne Wuerth, R.N., David Zurakowski, Ph.D., Alan Leichtner, M.D., Kathi Kemper, M.D., Vasundhara Tolia, M.D., and Athos Bousvaros, M.D. Center for Pediatric Gastroenterology, Royal Free Hospital, London, United Kingdom; Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Michigan, Detroit, Michigan; and Division of Gastroenterology, Hepatology and Nutrition and Center for Holistic Pediatric Education and Research, Children’s Hospital, Boston, Massachusetts
OBJECTIVES: We examined the use of complementary alternative medicine (CAM) in children and young adults with inflammatory bowel disease. METHODS: After validation of a questionnaire and completion of a pilot survey, children and young adults with inflammatory bowel disease were enrolled in three centers of pediatric gastroenterology (Boston, Detroit, and London). RESULTS: Two hundred eight questionnaires were completed in total (Boston, 120; Detroit, 37; London, 51). Ages ranged from 3.8 to 23.0 yr, 58% were male, 57% had Crohn’s disease, and 35% had ulcerative colitis. The frequency of CAM use was 41%. The most common CAMs were megavitamin therapy (19%), dietary supplements (17%), and herbal medicine (14%). Parental CAM use and the number of adverse effects from conventional medicines were predictors of CAM use (odds ratio ⫽ 1.9, 95% CI ⫽ 1.2–3.1, p ⫽ 0.02; odds ratio ⫽ 1.3, 95% CI ⫽ 1.2–1.5, p ⬍ 0.001, respectively). The most important reasons respondents gave for using CAM were side effects from prescribed medicines, prescribed medicines not working as well as they had hoped, and hoping for a cure. Fifty-nine percent of respondents not taking CAM were interested in learning more about it. CONCLUSIONS: In our survey over 40% of children with chronic inflammatory bowel disease used complementary medicine in addition to conventional therapies. Parental CAM use and number of adverse effects from conventional therapies were the only independent predictors of CAM use. Some complementary therapies have potential for adverse effects and for drug interactions with conventional treatments. Physicians should take a thorough history of CAM use in children with chronic inflammatory bowel disease. (Am J Gastroenterol 2002;97:382–388. © 2002 by Am. Coll. of Gastroenterology)
INTRODUCTION Children and young adults diagnosed with inflammatory bowel disease (IBD) face the prospect of dealing with a chronic illness through childhood, adolescence, and into adulthood. Relapses during childhood and adolescence often require repeated courses of corticosteroids and/or immunosuppressant medications. The adverse effects of these therapies, especially corticosteroids, are particularly problematic in the developing adolescent, when growth and body image are so critical. Because of the long duration and possible toxic effects of therapy, compliance with the conventional therapies in IBD can be a particular problem. Because of the lack of a definitive and well-tolerated treatment, children and their families may consider using complementary alternative medicine (CAM). In the last 10 yr there has been a dramatic increase in the use of complementary medicine worldwide (1–3). In 1990, the United States population was making more visits to practitioners of alternative medicine than to their primary care physicians. By 1997, out of pocket expenditure for alternative medicine in the United States had increased by over 45% to about $27 billion, similar to out of pocket expenditure for all United States physician services (3). In addition to this rising interest among the general population, CAM use is on the increase in patients with chronic diseases such as cancer and multiple sclerosis (4, 5). Patients may use CAM because they find these therapies more “natural” and because they may allow more choice and autonomy. The most frequent users within the adult population are those with a better education, a better income, and a holistic orientation to health. In addition, those with poorer health status and, particularly, chronic conditions such as back pain, anxiety, depression, and headaches use CAM more readily (3, 6). Although several studies have now addressed the use of CAM in adult patients, few have done so in children (7–10). Spigelblatt et al. (11) showed that 11% of over 1000 Canadian children attending routine outpatient clinics were using
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CAM, with chiropractic, homeopathy, naturopathy, and acupuncture accounting for over 80% of therapies used. In this study children who used CAM were older, had better educated mothers, and tended to have parents who also used CAM. Only about 20% of children in British outpatient clinics use CAM (12). Of these, 75% used homeopathy, aromatherapy, or osteopathy, with over 70% of respondents believing CAM had helped their child. CAM use may be especially common in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Early reports of CAM use in adults with IBD suggested a prevalence of 4 –13% (13, 14). However, Hilsden et al. (15, 16) surveyed their adult patients with IBD in Canada and found that 51% had used complementary therapies in the last 2 yr. However, only 33% of these were currently using CAM and only half of these did so for treatment of their IBD. Vitamin supplements and herbal remedies were the most commonly used therapies. A more recent international survey of adults with IBD (17) suggested that, on average, one in two patients were using CAM, with use being greater among North American patients than European ones. Borum et al. (18) reported that 33% of their adult patients with longstanding IBD were taking CAM. The predictors of CAM use in adults with IBD have been contradictory, but have included disease duration (⬎10 yr) and frequency of visits to their physicians. There have been no previous reports of CAM use in children with IBD. This international study seeks to a) establish the prevalence of CAM use in children and young adults with CD and UC and b) define the predictors of CAM use in these patients.
MATERIALS AND METHODS This is a cross-sectional questionnaire survey of children and young adults with IBD referred to three pediatric gastroenterology centers (Children’s Hospital, Boston, MA; Children’s Hospital of Michigan, Detroit, MI; and the Royal Free Hospital, London, United Kingdom). Patients aged 3.8 –23 yr were included once a diagnosis of IBD had been confirmed. All patients had the diagnosis of IBD made by standard clinical, radiographic, and histological criteria. They were required to have had the disease for a minimum of 3 months. Several measures were taken to minimize underreporting. Patients were all informed that questionnaires would be coded and analyzed anonymously. Data would not be passed on to their GI physicians unless specifically requested. Questionnaire Design In the absence of a generic instrument, a questionnaire directed at parents/caregivers was designed. Face validity of the instrument was assured by discussion with physicians caring for children with IBD (A.L., A.B., R.H.) and a practitioner of complementary medicine (K.K.) and by review of the available literature. Advice was sought from
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several homeopathic practitioners in Boston on the validity of questions about use of specific therapies in their field. The instrument consisted of 40 questions and took approximately 15 min to complete by self-administration. It sought to determine the prevalence of CAM use during the previous 12 months. Pilot Study During outpatient clinic or hospital admission, families attending Children’s Hospital, Boston completed 27 pilot questionnaires. After completion of the questionnaire, R.H. and the respondent reviewed both questions and answers to assess clarity, validity, and structure of the instrument. Results were then analyzed for data and comments about design and ease of use. Appropriate amendments were made to the questions and the structure of the instrument. In addition, experts in the field of questionnaire design (see Acknowledgments) then further modified the instrument before administration. Questionnaire Study The final instrument was designed for self-administration by parents, although a few young adults completed it themselves. This allowed patients to be enrolled during clinic visits and by mail. The survey was carried out between January 1 and October 31, 2000. Questionnaires were coded to ensure confidentiality during data extraction. Patients seen in the Division of Gastroenterology, Children’s Hospital, Boston during the last 2 yr were also sent a questionnaire if they had not completed one during a hospital or clinic visit in the first 3 months of the study. All questionnaires collected at the other centers were completed during clinic visits. The questionnaire used in the United Kingdom was minimally adjusted to allow for linguistic differences. Questionnaires were collected by specified investigators in each center (Detroit, A.W.; Boston, R.H.; London, N.A.). Data Analysis The data were entered into an ACCESS 97 database (Microsoft) by R.H., who also extracted all initial prevalence data. D.Z. carried out all other statistical analyses. Candidate predictors of CAM use were suggested a priori. These included age, sex, race, center, disease type (CD or UC), health status and disease severity (sick days, days off school), maternal education, family income, corticosteroid usage, number of adverse effects from conventional medications, and parental use of CAM. As many patients modify their diets with so-called lifestyle diets, and possibly do so on the advice of their physicians, we did not include dietary modification as a true CAM. In this study we defined “true” CAM users as those who used at least one complementary therapy, but excluded those who only modified their diet (e.g., lactose free, low residue, dairy and gluten free, caffeine free, wheat free, low fat and sugar). Univariate and multiple stepwise logistic regression analyses were performed to identify variables associated with
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Table 1. Patient Demographics Diagnosis UC CD Don’t know Age range Median age Sex and ethnicity Male Black White Other Parental education (mother/father) High school College Graduate school Income ($) ⬍39,999 40,000–79,999 ⬎80,000
Boston
Detroit
London
Total
n ⫽ 120 37 79 4 3.8–23 15.7 n ⫽ 120 72 3 109 8 n ⫽ 115/112 30/27 62/54 23/31 n ⫽ 101 14 41 46
n ⫽ 37 17 15 5 3.8–21 15.3 n ⫽ 36 16 11 23 2 n ⫽ 36/36 10/14 21/17 5/5 n ⫽ 32 9 11 12
n ⫽ 51 18 25 8 7.6–18 13.8 n ⫽ 50 32 2 39 9 n ⫽ 39/41 19/17 18/21 2/3 n ⫽ 41 14 27*
n ⫽ 208 72 119 17 3.8–23 15.0 n ⫽ 206 120 16 171 19 n ⫽ 190/189 59/58 101/92 30/39 n ⫽ 174 37 79 58
All numbers show raw data. n ⫽ number of respondents. *Includes all incomes ⬎ $80,000.
CAM usage. The backward elimination procedure based on the likelihood ratio test was used to determine multivariate predictors, and 95% CIs were calculated for significant variables (19). ps are two tailed, with an ␣ level of 0.05 considered statistically significant. Data analysis was completed with the SPSS software package (version 10.0, SPSS, Chicago, IL). The institutional review boards of Children’s Hospital, Boston; Children’s Hospital of Michigan; and the Royal Free Hospital, London approved the study.
RESULTS Two hundred eight questionnaires were completed in total. The numbers of questionnaires completed by respondents attending hospitals in Boston, Detroit, and London were 120 (58%), 37 (18%), and 51 (25%), respectively. Boston also mailed out a further 101 questionnaires, of which 65 were completed and returned (54% of the total for that center). Demographic data were analyzed individually for each center and for the whole sample (Table 1). Patients were all aged between 3.8 and 23 yr (median ⫽ 15.0). The age range at diagnosis was 0.5–20.17 and the duration of disease was comparable in all centers (3 months–16 yr, medians ⫽ 2.0 –2.8) (data not shown). Fifty-eight percent of patients were male and 83% were white. Fifty-seven percent of the whole sample had CD, and 35% had UC. Mothers answered 80% of questionnaires; fathers, 12%; and patients, 7%. Disease severity, as defined by surrogate markers of health status, was similar in all three groups. This was defined in terms of “days of sickness in last 14 days,” “nights in hospital in the last year,” and “days off school in the last year.” London patients reported the highest number of sickness days in the last 2 wk (30% had 14/14 days of sickness, compared to 12% and 15% in Boston and Detroit,
respectively). Patients in London also had more hospital admissions, days off school, and surgery than patients in the other two centers. Forty percent of London families said their child’s “state of health” was fair or poor, compared to only 13% and 17% in Boston and Detroit, respectively (Table 2). There were few differences in conventional therapy use between the three centers (Table 3). Sixty-seven percent of patients in Detroit had received corticosteroid therapy in the last 6 months, compared to 50% in London and 55% in Boston. The courses of corticosteroids tended to be longer in Detroit (40% ⬍ 6 months) than in London and Boston (30% and 29% ⬍ 6 months, respectively). There was no significant difference between units in the use of corticosteroids for over 6 months (20 –25%). Of all respondents, 44% and 50% were on azathioprine/6-mercaptopurine in Boston and London, respectively, whereas only 22% were on these immunosuppressants in Detroit. Patients in London received more exclusive enteral diets (30%) than in Detroit (19%) or Boston (6%). Other medications were prescribed in over 30% of all patients in the study. These included acid supTable 2. Disease Severity Days off school in last academic year ⬍5 6–15 ⬎15 Prior surgery State of health Excellent/very good/ good Fair/Poor
Boston
Detroit
London
Average
n ⫽ 118
n ⫽ 37
n ⫽ 51
n ⫽ 206
74 11 15 17 n ⫽ 119 87
49 30 21 5 n ⫽ 35 83
27 20 53 22 n ⫽ 51 63
50 20 30 15 n ⫽ 205 78
13
17
37
22
All numbers in percentages. n ⫽ number of respondents.
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Table 3. Prescribed Medicine Use
Oral steroid therapy ⬍6 mo ⬎6 mo 5-ASA therapy Azathioprine/6-MP therapy Antibiotics Methotrexate/infliximab Other (ranitidine, iron, folic acid, omeprazole, lansoprazole, zinc, vitamin D, thalidomide, antacids, budesonide, cisapride, laxatives) Exclusive enteral diet p.o./NG supplements
Boston (n ⫽ 120)
Detroit (n ⫽ 37)
London (n ⫽ 50)
Average
55 29 25 81 44 31 6 29
67 41 24 97 22 24 8 51
50 30 20 86 50 26 0 26
57 33 23 88 39 27 5 35
6 33
19 40
30 42
18 39
All numbers in percentages. % values represent the percentage of respondents at each site (e.g., 55% of 120 respondents had used oral steroid therapy over the last 12 mo in Boston). 5-ASA ⫽ 5-aminosalicylic acid, 6-MP ⫽ 6-mercaptopurine, n ⫽ number of respondents.
pressors (histamine-2 blockers and proton pump inhibitors), iron and folic acid supplements, and motility agents (cisapride). Without including dietary supplementation as a “true” complementary therapy in IBD, we found 41% of all respondents used a true CAM in addition to conventional therapies (Table 4). Of all our respondents, 19% used megavitamin/mineral therapy (this question stem specifically stated that this therapy did not include the use of “One-a-Day” multivitamin supplements, and listed the following examples: magnesium, calcium, iron, selenium, vitamin C, vitamin B6). Dietary supplements were used by 17% and included glutamine, glucosamine, fish oils, prebiotics, nicotinamide, and papaya enzyme. Herbal medicine use (14% of respondents) included aloe vera, evening primrose oil, Chinese herbs, flaxseed oil, borageseed oil, cats claw, OPC-3 (grapeseed/pinebark extract), cayenne capsules, colostrum, herbal teas, licorice root, and lobelia. Environmental and lifestyle changes were made by 10% of patients; these included allergen reduction, music and aromatherapy, bioresonance, exercise, and prayer. Homeopathic remedies were used by 6%, and included arnica and phosphorus-containing compounds. (Dietary modifications were made by 35% of all respondents but were not included in our analysis, as stated above.)
Respondents using CAMs felt they were more than “a little” helpful in their treatment (mean ⫽ 2.25; 1 ⫽ not at all, 2 ⫽ a little, 3 ⫽ very helpful). CAMs recommended by respondents included acupuncture (five patients), massage (three), homeopathy (three), herbs (three), fish oil (two), and healer (one). Therapies that respondents advised against included seeing a physician (two), seeing a chiropractor (three), acupuncture (two), homeopath (two), herbs (one), hypnosis (one), and all CAM therapies (two). Only 8% of doctors, but 24% of patients, had initiated a discussion about CAM (data not shown). Reasons given by respondents for using CAM are shown in Table 5, and included wanting to believe better, hoping for a cure, and disappointment with conventional therapies. Univariate logistic regression analysis revealed two variables associated with CAM usage: parental CAM usage (odds ratio ⫽ 1.9, 95% CI ⫽ 1.2–3.1, p ⫽ 0.02) and number of adverse effects (odds ratio ⫽ 1.3, 95% CI ⫽ 1.2–1.5, p ⬍ 0.001). This suggests that CAM users have a greater number of adverse effects from conventional medicines and that individuals whose parents use alternative medicine are more likely to be users themselves (nearly twice as likely). However, results of the multivariate analysis indicate that the number of adverse effects from conventional therapies was the only significant predictor that differentiates CAM users
Table 4. CAM Use
Table 5. Reasons for Choosing CAM Boston Detroit London Total (n ⫽ 120) (n ⫽ 37) (n ⫽ 51) (n ⫽ 208)
“True CAM users” Megavitamin Dietary supplements Herbal medicines Environmental change Acupuncture Homeopathy Probiotics Hypnosis Biofeedback Healer Massage All numbers in percentages.
38 19 12 9 8 7 4 7 4 1 3 5
49 30 27 24 19 0 3 8 11 3 5 5
41 12 22 18 8 8 14 2 2 6 8 0
41 19 17 14 10 6 6 6 5 2 4 4
Mean Want to feel better Hoped for a cure Prescribed medicines didn’t work as well as hoped Side effects of prescribed medicines Wanted more control Want more natural therapy Taking too many medicines Recommended by doctor Therapy made more sense Consistent with personal values Advised by friends and family Read about it on internet Saw an advertisement
4.6 4.3 4.1 4.1 4.0 3.9 3.9 3.5 3.4 3.0 2.3 2.3 1.5
5 ⫽ very important; 1 ⫽ not important. Minimum of 40 respondents/category.
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Table 6. Variables Associated With Alternative Medicine Usage Multiple Stepwise Logistic Regression Univariate p Age Sex Race Disease (CD vs UC) Health status Sick days Days off from school Maternal education Income Steroid use ⬎ 6 mo Parental CAM usage Study center No. of side effects*
0.16 0.15 0.58 0.39 0.07 0.35 0.55 0.62 0.44 0.22 0.02 0.49 ⬍0.001
Odds Ratio
95% CI
1.9
1.2–3.1
1.3
1.2–1.5
p 0.08 0.37 0.48 0.45 0.44 0.93 0.34 0.14 0.29 0.47 0.10 0.58 0.002
* Treated as a continuous variable.
and nonusers. This was independent of age, sex, race, center, disease, health status, sickness days, days off school, maternal education, income, corticosteroid usage, and parental CAM usage. Three adverse effects were listed by over 30% of patients utilizing CAM. These were “moodiness,” “weight gain,” and “headaches.” Interestingly, in considering the number of adverse effects as a categorical predictor (yes/no), the odds of being a CAM user were estimated to be 2.5 times higher for those who had adverse effects (odds ratio ⫽ 2.5, 95% CI ⫽ 1.5– 4.2, p ⫽ 0.008). As indicated in Table 6, when treating adverse effects as a continuous variable, the odds of being a user were 30% higher (20 –50% according to the 95% CI) for each additional side effect.
DISCUSSION This is the first study to describe the use of CAM in children and young adults with IBD. Over 40% use at least one CAM in addition to their conventional therapies, with maternal hopes for a child’s improved health and a possible cure being the most important reasons for using CAM. The only significant predictor of CAM use was the number of adverse effects experienced from conventional medicines. The odds of using CAM increased by 30% with each additional adverse effect. On univariate analysis, parental CAM use was an independent predictor of CAM use in the child with chronic IBD. Our findings suggest a much greater use of CAM in children with IBD than has been reported in adults with IBD (13–15). Despite the well-described increase in the use of CAM, the use by almost one in two children with IBD is surprising, particularly as dietary modification was not included in our definition of CAM. The collection of questionnaires from outpatient clinics and by mail ensured a representative sample. However, families in London and Detroit completed the questionnaires during hospital or outpatient visits, thus favoring the
inclusion of patients with more severe disease. In Detroit, outpatient visits were for routine follow-up. In the United Kingdom, patients with milder disease are often seen outside tertiary centers, thereby further skewing that sample to include children with more severe disease. Both factors are likely to contribute to the greater disease severity seen in the United Kingdom patient group. Overall, however, the entire sample is likely to be representative of children with IBD, irrespective of where they receive their care. The selfadministered questionnaire also assessed the parental perception of a child’s general state of health as a predictor of CAM use, although this is not a true reflection of disease severity. As a prevalence study, we did not further investigate the efficacy or possible adverse effects of the reported CAM. Further work is required to investigate the individual therapies used by these patients. Although there were no adverse events encountered in this study, these have been reported at length (20 –22). Knowledge of CAM use is important in view of the continuing lack of quality control over “dietary supplements” (23) and their reported interactions with conventional therapies (24, 25). Many of the therapies used by the patients in this study have potentially important adverse effects (26). Aloe vera has a laxative effect, and evening primrose oil and bovine colostrum can cause nausea and gastric discomfort. Borageseed oil has antiplatelet effects, whereas cat’s claw has been described to cause hypotension. Cayenne capsules cause gastric irritation and hepatorenal toxicity and lobelia may cause nausea, vomiting, dizziness, and diarrhea. Glycyrrhizin (in licorice root) can lead to amenorrhoea, diarrhea, and pseudohypoaldosteronism, whereas it is also reported to increase plasma concentrations of prednisolone (27). There are several interactions particularly relevant to patients with IBD. Betel nut contains arecoline, a cholinergic alkaloid that has been shown to counteract the effects of prednisolone (28). St John’s wort can reduce the serum concentrations of cyclosporin (29, 30). Herbs with immunostimulatory effects (echinacea, licorice, vitamin E, zinc) should not be given with immunosuppressants (24). However, despite the many reported adverse effects, the true incidence of CAM-induced adverse effects is unknown. Systematic review clearly indicates a greater use of CAM among children with chronic, incurable conditions (31, 32). However, there are few data to support any of the therapies in the treatment of IBD. With the increasing demand for CAM from families of children with chronic IBD, we urgently need quality data to better inform both doctors and their patients. In our study, 59% of respondents not already using CAM were interested in finding out more about its use, yet only 8% of doctors had initiated a discussion about CAM with their patients. Only 24% of patients using CAM had informed their doctor that they were doing so. One of the more important reasons for choosing CAM in our study was the need to have more control over therapy. This and the easier access to a wide range of therapies and
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practitioners also makes CAM significantly more attractive than conventional therapy. The access to more personalized and frequent advice is another factor that has been shown to be important in managing chronic bowel diseases. Patients with UC respond better to placebos in randomized trials if they are seen on more than three occasions during follow-up (33). It is well established in cancer medicine that familiarity with alternative therapies is necessary to communicate knowledgeably with patients and provide optimal guidance (34). Physicians caring for children with other chronic illnesses need to be aware of all the therapeutic choices that are available to their patients. This is the first study to document the widespread use of complementary alternative therapies in children with IBD. The absence of unbiased data on efficacy and the ongoing concerns about adverse effects should stimulate more pediatricians to ask their patients about CAM use. Talking about CAM with patients may minimize the risks (35). The finding that the number of adverse effects from conventional medicines is the most significant predictor of CAM use in these children is not unexpected. It thus appears that CAM is used not so much as a result of disease severity, but more in response to the adverse effects of conventional therapies. These results have important implications for gastroenterologists, health care payers, and everyone involved in the long term management of these children.
ACKNOWLEDGMENTS We thank the following for their invaluable advice in developing the questionnaire: Gary N. Siperstein, Ph.D., Director of the Center for Social Development and Education, University of Massachusetts, Boston, MA, and Thomas Inui, M.D., Sc.M., Lecturer, Harvard School of Public Health, Department of Ambulatory Care and Prevention, Boston, MA. A.B. was funded in part by the Crohn’s and Colitis Foundation of America, and R.H. gratefully acknowledges funds provided by the National Institutes of Health “Training Grant in Pediatric Gastroenterology and Nutrition” (#T32-DK07477–16). Reprint requests and correspondence: Robert B. Heuschkel, M.B., B.S., M.R.C.P.C.H., Center for Pediatric Gastroenterology, Royal Free Hospital, Pond Street, Hampstead, London, UK, NW3 2QG. Received Apr. 26, 2001; accepted Aug. 14, 2001.
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Vol. 97, No. 2, 2002 ISSN 0002-9270/02/$22.00 PII S0002-9270(01)04036-9
Complementary Medicine Use in Children and Young Adults With Inflammatory Bowel Disease Robert Heuschkel, M.B.B.S., M.R.C.P.C.H., Nadeem Afzal, M.B.B.S., M.R.C.P., Anne Wuerth, R.N., David Zurakowski, Ph.D., Alan Leichtner, M.D., Kathi Kemper, M.D., Vasundhara Tolia, M.D., and Athos Bousvaros, M.D. Center for Pediatric Gastroenterology, Royal Free Hospital, London, United Kingdom; Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Michigan, Detroit, Michigan; and Division of Gastroenterology, Hepatology and Nutrition and Center for Holistic Pediatric Education and Research, Children’s Hospital, Boston, Massachusetts
OBJECTIVES: We examined the use of complementary alternative medicine (CAM) in children and young adults with inflammatory bowel disease. METHODS: After validation of a questionnaire and completion of a pilot survey, children and young adults with inflammatory bowel disease were enrolled in three centers of pediatric gastroenterology (Boston, Detroit, and London). RESULTS: Two hundred eight questionnaires were completed in total (Boston, 120; Detroit, 37; London, 51). Ages ranged from 3.8 to 23.0 yr, 58% were male, 57% had Crohn’s disease, and 35% had ulcerative colitis. The frequency of CAM use was 41%. The most common CAMs were megavitamin therapy (19%), dietary supplements (17%), and herbal medicine (14%). Parental CAM use and the number of adverse effects from conventional medicines were predictors of CAM use (odds ratio ⫽ 1.9, 95% CI ⫽ 1.2–3.1, p ⫽ 0.02; odds ratio ⫽ 1.3, 95% CI ⫽ 1.2–1.5, p ⬍ 0.001, respectively). The most important reasons respondents gave for using CAM were side effects from prescribed medicines, prescribed medicines not working as well as they had hoped, and hoping for a cure. Fifty-nine percent of respondents not taking CAM were interested in learning more about it. CONCLUSIONS: In our survey over 40% of children with chronic inflammatory bowel disease used complementary medicine in addition to conventional therapies. Parental CAM use and number of adverse effects from conventional therapies were the only independent predictors of CAM use. Some complementary therapies have potential for adverse effects and for drug interactions with conventional treatments. Physicians should take a thorough history of CAM use in children with chronic inflammatory bowel disease. (Am J Gastroenterol 2002;97:382–388. © 2002 by Am. Coll. of Gastroenterology)
INTRODUCTION Children and young adults diagnosed with inflammatory bowel disease (IBD) face the prospect of dealing with a chronic illness through childhood, adolescence, and into adulthood. Relapses during childhood and adolescence often require repeated courses of corticosteroids and/or immunosuppressant medications. The adverse effects of these therapies, especially corticosteroids, are particularly problematic in the developing adolescent, when growth and body image are so critical. Because of the long duration and possible toxic effects of therapy, compliance with the conventional therapies in IBD can be a particular problem. Because of the lack of a definitive and well-tolerated treatment, children and their families may consider using complementary alternative medicine (CAM). In the last 10 yr there has been a dramatic increase in the use of complementary medicine worldwide (1–3). In 1990, the United States population was making more visits to practitioners of alternative medicine than to their primary care physicians. By 1997, out of pocket expenditure for alternative medicine in the United States had increased by over 45% to about $27 billion, similar to out of pocket expenditure for all United States physician services (3). In addition to this rising interest among the general population, CAM use is on the increase in patients with chronic diseases such as cancer and multiple sclerosis (4, 5). Patients may use CAM because they find these therapies more “natural” and because they may allow more choice and autonomy. The most frequent users within the adult population are those with a better education, a better income, and a holistic orientation to health. In addition, those with poorer health status and, particularly, chronic conditions such as back pain, anxiety, depression, and headaches use CAM more readily (3, 6). Although several studies have now addressed the use of CAM in adult patients, few have done so in children (7–10). Spigelblatt et al. (11) showed that 11% of over 1000 Canadian children attending routine outpatient clinics were using
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CAM, with chiropractic, homeopathy, naturopathy, and acupuncture accounting for over 80% of therapies used. In this study children who used CAM were older, had better educated mothers, and tended to have parents who also used CAM. Only about 20% of children in British outpatient clinics use CAM (12). Of these, 75% used homeopathy, aromatherapy, or osteopathy, with over 70% of respondents believing CAM had helped their child. CAM use may be especially common in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Early reports of CAM use in adults with IBD suggested a prevalence of 4 –13% (13, 14). However, Hilsden et al. (15, 16) surveyed their adult patients with IBD in Canada and found that 51% had used complementary therapies in the last 2 yr. However, only 33% of these were currently using CAM and only half of these did so for treatment of their IBD. Vitamin supplements and herbal remedies were the most commonly used therapies. A more recent international survey of adults with IBD (17) suggested that, on average, one in two patients were using CAM, with use being greater among North American patients than European ones. Borum et al. (18) reported that 33% of their adult patients with longstanding IBD were taking CAM. The predictors of CAM use in adults with IBD have been contradictory, but have included disease duration (⬎10 yr) and frequency of visits to their physicians. There have been no previous reports of CAM use in children with IBD. This international study seeks to a) establish the prevalence of CAM use in children and young adults with CD and UC and b) define the predictors of CAM use in these patients.
MATERIALS AND METHODS This is a cross-sectional questionnaire survey of children and young adults with IBD referred to three pediatric gastroenterology centers (Children’s Hospital, Boston, MA; Children’s Hospital of Michigan, Detroit, MI; and the Royal Free Hospital, London, United Kingdom). Patients aged 3.8 –23 yr were included once a diagnosis of IBD had been confirmed. All patients had the diagnosis of IBD made by standard clinical, radiographic, and histological criteria. They were required to have had the disease for a minimum of 3 months. Several measures were taken to minimize underreporting. Patients were all informed that questionnaires would be coded and analyzed anonymously. Data would not be passed on to their GI physicians unless specifically requested. Questionnaire Design In the absence of a generic instrument, a questionnaire directed at parents/caregivers was designed. Face validity of the instrument was assured by discussion with physicians caring for children with IBD (A.L., A.B., R.H.) and a practitioner of complementary medicine (K.K.) and by review of the available literature. Advice was sought from
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several homeopathic practitioners in Boston on the validity of questions about use of specific therapies in their field. The instrument consisted of 40 questions and took approximately 15 min to complete by self-administration. It sought to determine the prevalence of CAM use during the previous 12 months. Pilot Study During outpatient clinic or hospital admission, families attending Children’s Hospital, Boston completed 27 pilot questionnaires. After completion of the questionnaire, R.H. and the respondent reviewed both questions and answers to assess clarity, validity, and structure of the instrument. Results were then analyzed for data and comments about design and ease of use. Appropriate amendments were made to the questions and the structure of the instrument. In addition, experts in the field of questionnaire design (see Acknowledgments) then further modified the instrument before administration. Questionnaire Study The final instrument was designed for self-administration by parents, although a few young adults completed it themselves. This allowed patients to be enrolled during clinic visits and by mail. The survey was carried out between January 1 and October 31, 2000. Questionnaires were coded to ensure confidentiality during data extraction. Patients seen in the Division of Gastroenterology, Children’s Hospital, Boston during the last 2 yr were also sent a questionnaire if they had not completed one during a hospital or clinic visit in the first 3 months of the study. All questionnaires collected at the other centers were completed during clinic visits. The questionnaire used in the United Kingdom was minimally adjusted to allow for linguistic differences. Questionnaires were collected by specified investigators in each center (Detroit, A.W.; Boston, R.H.; London, N.A.). Data Analysis The data were entered into an ACCESS 97 database (Microsoft) by R.H., who also extracted all initial prevalence data. D.Z. carried out all other statistical analyses. Candidate predictors of CAM use were suggested a priori. These included age, sex, race, center, disease type (CD or UC), health status and disease severity (sick days, days off school), maternal education, family income, corticosteroid usage, number of adverse effects from conventional medications, and parental use of CAM. As many patients modify their diets with so-called lifestyle diets, and possibly do so on the advice of their physicians, we did not include dietary modification as a true CAM. In this study we defined “true” CAM users as those who used at least one complementary therapy, but excluded those who only modified their diet (e.g., lactose free, low residue, dairy and gluten free, caffeine free, wheat free, low fat and sugar). Univariate and multiple stepwise logistic regression analyses were performed to identify variables associated with
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Table 1. Patient Demographics Diagnosis UC CD Don’t know Age range Median age Sex and ethnicity Male Black White Other Parental education (mother/father) High school College Graduate school Income ($) ⬍39,999 40,000–79,999 ⬎80,000
Boston
Detroit
London
Total
n ⫽ 120 37 79 4 3.8–23 15.7 n ⫽ 120 72 3 109 8 n ⫽ 115/112 30/27 62/54 23/31 n ⫽ 101 14 41 46
n ⫽ 37 17 15 5 3.8–21 15.3 n ⫽ 36 16 11 23 2 n ⫽ 36/36 10/14 21/17 5/5 n ⫽ 32 9 11 12
n ⫽ 51 18 25 8 7.6–18 13.8 n ⫽ 50 32 2 39 9 n ⫽ 39/41 19/17 18/21 2/3 n ⫽ 41 14 27*
n ⫽ 208 72 119 17 3.8–23 15.0 n ⫽ 206 120 16 171 19 n ⫽ 190/189 59/58 101/92 30/39 n ⫽ 174 37 79 58
All numbers show raw data. n ⫽ number of respondents. *Includes all incomes ⬎ $80,000.
CAM usage. The backward elimination procedure based on the likelihood ratio test was used to determine multivariate predictors, and 95% CIs were calculated for significant variables (19). ps are two tailed, with an ␣ level of 0.05 considered statistically significant. Data analysis was completed with the SPSS software package (version 10.0, SPSS, Chicago, IL). The institutional review boards of Children’s Hospital, Boston; Children’s Hospital of Michigan; and the Royal Free Hospital, London approved the study.
RESULTS Two hundred eight questionnaires were completed in total. The numbers of questionnaires completed by respondents attending hospitals in Boston, Detroit, and London were 120 (58%), 37 (18%), and 51 (25%), respectively. Boston also mailed out a further 101 questionnaires, of which 65 were completed and returned (54% of the total for that center). Demographic data were analyzed individually for each center and for the whole sample (Table 1). Patients were all aged between 3.8 and 23 yr (median ⫽ 15.0). The age range at diagnosis was 0.5–20.17 and the duration of disease was comparable in all centers (3 months–16 yr, medians ⫽ 2.0 –2.8) (data not shown). Fifty-eight percent of patients were male and 83% were white. Fifty-seven percent of the whole sample had CD, and 35% had UC. Mothers answered 80% of questionnaires; fathers, 12%; and patients, 7%. Disease severity, as defined by surrogate markers of health status, was similar in all three groups. This was defined in terms of “days of sickness in last 14 days,” “nights in hospital in the last year,” and “days off school in the last year.” London patients reported the highest number of sickness days in the last 2 wk (30% had 14/14 days of sickness, compared to 12% and 15% in Boston and Detroit,
respectively). Patients in London also had more hospital admissions, days off school, and surgery than patients in the other two centers. Forty percent of London families said their child’s “state of health” was fair or poor, compared to only 13% and 17% in Boston and Detroit, respectively (Table 2). There were few differences in conventional therapy use between the three centers (Table 3). Sixty-seven percent of patients in Detroit had received corticosteroid therapy in the last 6 months, compared to 50% in London and 55% in Boston. The courses of corticosteroids tended to be longer in Detroit (40% ⬍ 6 months) than in London and Boston (30% and 29% ⬍ 6 months, respectively). There was no significant difference between units in the use of corticosteroids for over 6 months (20 –25%). Of all respondents, 44% and 50% were on azathioprine/6-mercaptopurine in Boston and London, respectively, whereas only 22% were on these immunosuppressants in Detroit. Patients in London received more exclusive enteral diets (30%) than in Detroit (19%) or Boston (6%). Other medications were prescribed in over 30% of all patients in the study. These included acid supTable 2. Disease Severity Days off school in last academic year ⬍5 6–15 ⬎15 Prior surgery State of health Excellent/very good/ good Fair/Poor
Boston
Detroit
London
Average
n ⫽ 118
n ⫽ 37
n ⫽ 51
n ⫽ 206
74 11 15 17 n ⫽ 119 87
49 30 21 5 n ⫽ 35 83
27 20 53 22 n ⫽ 51 63
50 20 30 15 n ⫽ 205 78
13
17
37
22
All numbers in percentages. n ⫽ number of respondents.
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Table 3. Prescribed Medicine Use
Oral steroid therapy ⬍6 mo ⬎6 mo 5-ASA therapy Azathioprine/6-MP therapy Antibiotics Methotrexate/infliximab Other (ranitidine, iron, folic acid, omeprazole, lansoprazole, zinc, vitamin D, thalidomide, antacids, budesonide, cisapride, laxatives) Exclusive enteral diet p.o./NG supplements
Boston (n ⫽ 120)
Detroit (n ⫽ 37)
London (n ⫽ 50)
Average
55 29 25 81 44 31 6 29
67 41 24 97 22 24 8 51
50 30 20 86 50 26 0 26
57 33 23 88 39 27 5 35
6 33
19 40
30 42
18 39
All numbers in percentages. % values represent the percentage of respondents at each site (e.g., 55% of 120 respondents had used oral steroid therapy over the last 12 mo in Boston). 5-ASA ⫽ 5-aminosalicylic acid, 6-MP ⫽ 6-mercaptopurine, n ⫽ number of respondents.
pressors (histamine-2 blockers and proton pump inhibitors), iron and folic acid supplements, and motility agents (cisapride). Without including dietary supplementation as a “true” complementary therapy in IBD, we found 41% of all respondents used a true CAM in addition to conventional therapies (Table 4). Of all our respondents, 19% used megavitamin/mineral therapy (this question stem specifically stated that this therapy did not include the use of “One-a-Day” multivitamin supplements, and listed the following examples: magnesium, calcium, iron, selenium, vitamin C, vitamin B6). Dietary supplements were used by 17% and included glutamine, glucosamine, fish oils, prebiotics, nicotinamide, and papaya enzyme. Herbal medicine use (14% of respondents) included aloe vera, evening primrose oil, Chinese herbs, flaxseed oil, borageseed oil, cats claw, OPC-3 (grapeseed/pinebark extract), cayenne capsules, colostrum, herbal teas, licorice root, and lobelia. Environmental and lifestyle changes were made by 10% of patients; these included allergen reduction, music and aromatherapy, bioresonance, exercise, and prayer. Homeopathic remedies were used by 6%, and included arnica and phosphorus-containing compounds. (Dietary modifications were made by 35% of all respondents but were not included in our analysis, as stated above.)
Respondents using CAMs felt they were more than “a little” helpful in their treatment (mean ⫽ 2.25; 1 ⫽ not at all, 2 ⫽ a little, 3 ⫽ very helpful). CAMs recommended by respondents included acupuncture (five patients), massage (three), homeopathy (three), herbs (three), fish oil (two), and healer (one). Therapies that respondents advised against included seeing a physician (two), seeing a chiropractor (three), acupuncture (two), homeopath (two), herbs (one), hypnosis (one), and all CAM therapies (two). Only 8% of doctors, but 24% of patients, had initiated a discussion about CAM (data not shown). Reasons given by respondents for using CAM are shown in Table 5, and included wanting to believe better, hoping for a cure, and disappointment with conventional therapies. Univariate logistic regression analysis revealed two variables associated with CAM usage: parental CAM usage (odds ratio ⫽ 1.9, 95% CI ⫽ 1.2–3.1, p ⫽ 0.02) and number of adverse effects (odds ratio ⫽ 1.3, 95% CI ⫽ 1.2–1.5, p ⬍ 0.001). This suggests that CAM users have a greater number of adverse effects from conventional medicines and that individuals whose parents use alternative medicine are more likely to be users themselves (nearly twice as likely). However, results of the multivariate analysis indicate that the number of adverse effects from conventional therapies was the only significant predictor that differentiates CAM users
Table 4. CAM Use
Table 5. Reasons for Choosing CAM Boston Detroit London Total (n ⫽ 120) (n ⫽ 37) (n ⫽ 51) (n ⫽ 208)
“True CAM users” Megavitamin Dietary supplements Herbal medicines Environmental change Acupuncture Homeopathy Probiotics Hypnosis Biofeedback Healer Massage All numbers in percentages.
38 19 12 9 8 7 4 7 4 1 3 5
49 30 27 24 19 0 3 8 11 3 5 5
41 12 22 18 8 8 14 2 2 6 8 0
41 19 17 14 10 6 6 6 5 2 4 4
Mean Want to feel better Hoped for a cure Prescribed medicines didn’t work as well as hoped Side effects of prescribed medicines Wanted more control Want more natural therapy Taking too many medicines Recommended by doctor Therapy made more sense Consistent with personal values Advised by friends and family Read about it on internet Saw an advertisement
4.6 4.3 4.1 4.1 4.0 3.9 3.9 3.5 3.4 3.0 2.3 2.3 1.5
5 ⫽ very important; 1 ⫽ not important. Minimum of 40 respondents/category.
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Table 6. Variables Associated With Alternative Medicine Usage Multiple Stepwise Logistic Regression Univariate p Age Sex Race Disease (CD vs UC) Health status Sick days Days off from school Maternal education Income Steroid use ⬎ 6 mo Parental CAM usage Study center No. of side effects*
0.16 0.15 0.58 0.39 0.07 0.35 0.55 0.62 0.44 0.22 0.02 0.49 ⬍0.001
Odds Ratio
95% CI
1.9
1.2–3.1
1.3
1.2–1.5
p 0.08 0.37 0.48 0.45 0.44 0.93 0.34 0.14 0.29 0.47 0.10 0.58 0.002
* Treated as a continuous variable.
and nonusers. This was independent of age, sex, race, center, disease, health status, sickness days, days off school, maternal education, income, corticosteroid usage, and parental CAM usage. Three adverse effects were listed by over 30% of patients utilizing CAM. These were “moodiness,” “weight gain,” and “headaches.” Interestingly, in considering the number of adverse effects as a categorical predictor (yes/no), the odds of being a CAM user were estimated to be 2.5 times higher for those who had adverse effects (odds ratio ⫽ 2.5, 95% CI ⫽ 1.5– 4.2, p ⫽ 0.008). As indicated in Table 6, when treating adverse effects as a continuous variable, the odds of being a user were 30% higher (20 –50% according to the 95% CI) for each additional side effect.
DISCUSSION This is the first study to describe the use of CAM in children and young adults with IBD. Over 40% use at least one CAM in addition to their conventional therapies, with maternal hopes for a child’s improved health and a possible cure being the most important reasons for using CAM. The only significant predictor of CAM use was the number of adverse effects experienced from conventional medicines. The odds of using CAM increased by 30% with each additional adverse effect. On univariate analysis, parental CAM use was an independent predictor of CAM use in the child with chronic IBD. Our findings suggest a much greater use of CAM in children with IBD than has been reported in adults with IBD (13–15). Despite the well-described increase in the use of CAM, the use by almost one in two children with IBD is surprising, particularly as dietary modification was not included in our definition of CAM. The collection of questionnaires from outpatient clinics and by mail ensured a representative sample. However, families in London and Detroit completed the questionnaires during hospital or outpatient visits, thus favoring the
inclusion of patients with more severe disease. In Detroit, outpatient visits were for routine follow-up. In the United Kingdom, patients with milder disease are often seen outside tertiary centers, thereby further skewing that sample to include children with more severe disease. Both factors are likely to contribute to the greater disease severity seen in the United Kingdom patient group. Overall, however, the entire sample is likely to be representative of children with IBD, irrespective of where they receive their care. The selfadministered questionnaire also assessed the parental perception of a child’s general state of health as a predictor of CAM use, although this is not a true reflection of disease severity. As a prevalence study, we did not further investigate the efficacy or possible adverse effects of the reported CAM. Further work is required to investigate the individual therapies used by these patients. Although there were no adverse events encountered in this study, these have been reported at length (20 –22). Knowledge of CAM use is important in view of the continuing lack of quality control over “dietary supplements” (23) and their reported interactions with conventional therapies (24, 25). Many of the therapies used by the patients in this study have potentially important adverse effects (26). Aloe vera has a laxative effect, and evening primrose oil and bovine colostrum can cause nausea and gastric discomfort. Borageseed oil has antiplatelet effects, whereas cat’s claw has been described to cause hypotension. Cayenne capsules cause gastric irritation and hepatorenal toxicity and lobelia may cause nausea, vomiting, dizziness, and diarrhea. Glycyrrhizin (in licorice root) can lead to amenorrhoea, diarrhea, and pseudohypoaldosteronism, whereas it is also reported to increase plasma concentrations of prednisolone (27). There are several interactions particularly relevant to patients with IBD. Betel nut contains arecoline, a cholinergic alkaloid that has been shown to counteract the effects of prednisolone (28). St John’s wort can reduce the serum concentrations of cyclosporin (29, 30). Herbs with immunostimulatory effects (echinacea, licorice, vitamin E, zinc) should not be given with immunosuppressants (24). However, despite the many reported adverse effects, the true incidence of CAM-induced adverse effects is unknown. Systematic review clearly indicates a greater use of CAM among children with chronic, incurable conditions (31, 32). However, there are few data to support any of the therapies in the treatment of IBD. With the increasing demand for CAM from families of children with chronic IBD, we urgently need quality data to better inform both doctors and their patients. In our study, 59% of respondents not already using CAM were interested in finding out more about its use, yet only 8% of doctors had initiated a discussion about CAM with their patients. Only 24% of patients using CAM had informed their doctor that they were doing so. One of the more important reasons for choosing CAM in our study was the need to have more control over therapy. This and the easier access to a wide range of therapies and
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practitioners also makes CAM significantly more attractive than conventional therapy. The access to more personalized and frequent advice is another factor that has been shown to be important in managing chronic bowel diseases. Patients with UC respond better to placebos in randomized trials if they are seen on more than three occasions during follow-up (33). It is well established in cancer medicine that familiarity with alternative therapies is necessary to communicate knowledgeably with patients and provide optimal guidance (34). Physicians caring for children with other chronic illnesses need to be aware of all the therapeutic choices that are available to their patients. This is the first study to document the widespread use of complementary alternative therapies in children with IBD. The absence of unbiased data on efficacy and the ongoing concerns about adverse effects should stimulate more pediatricians to ask their patients about CAM use. Talking about CAM with patients may minimize the risks (35). The finding that the number of adverse effects from conventional medicines is the most significant predictor of CAM use in these children is not unexpected. It thus appears that CAM is used not so much as a result of disease severity, but more in response to the adverse effects of conventional therapies. These results have important implications for gastroenterologists, health care payers, and everyone involved in the long term management of these children.
ACKNOWLEDGMENTS We thank the following for their invaluable advice in developing the questionnaire: Gary N. Siperstein, Ph.D., Director of the Center for Social Development and Education, University of Massachusetts, Boston, MA, and Thomas Inui, M.D., Sc.M., Lecturer, Harvard School of Public Health, Department of Ambulatory Care and Prevention, Boston, MA. A.B. was funded in part by the Crohn’s and Colitis Foundation of America, and R.H. gratefully acknowledges funds provided by the National Institutes of Health “Training Grant in Pediatric Gastroenterology and Nutrition” (#T32-DK07477–16). Reprint requests and correspondence: Robert B. Heuschkel, M.B., B.S., M.R.C.P.C.H., Center for Pediatric Gastroenterology, Royal Free Hospital, Pond Street, Hampstead, London, UK, NW3 2QG. Received Apr. 26, 2001; accepted Aug. 14, 2001.
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