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Dae-Won Jun, Oh-Young Lee, Ho-Joo Yoon, Hang-Lak Lee, Ho-Soon Choi, Byung-Chul Yoon, Min-Ho Lee, Dong-Hoo Lee, Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea Seok-Hwa Lee, Department of Food and Nutrition, College of Human Ecology, Hanyang University, Seoul, Korea Sang-Hoen Cho, Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, South Korea Supported by a grant from the Korea Society of Neurogastroenterology and Motility Research Funds (project No. 2003530). Correspondence to: Oh-Young Lee, Department of Internal Medicine, College of Medicine, Hanyang University Hospital, Seoul, South Korea 17 Haengdang-dong, Sungdong-ku, Seoul 133-791, Korea. leeoy@hanyang.ac.kr Telephone: +82-2-22908343 Fax: +82-2-2298-9183 Received: 2005-07-23 Accepted: 2005-10-10
Abstract AIM: To correlate the clinical features of treated and untreated patients with irritable bowel syndrome (IBS) to the results of skin prick test (SPT) for food and inhalant allergens.
METHODS: We recruited 105 subjects to form three different target groups: treated group (n = 44) undergoing treatment for IBS, untreated group (n = 31) meeting the Rome II criteria without treatment for IBS, control group (n = 30) with no IBS symptoms.
RESULTS: SPT results were different among the three groups in which SPT was positive in 17 (38.6%) treated patients, in 5 (16.1%) untreated patients and in 1 (3.3%) control (P < 0.01). The number of positive SPTs was greater in the IBS group than in the control group (P < 0.001). The number of positive food SPTs was higher in the treated IBS group than in the untreated IBS group (P = 0.03).
CONCLUSION: Positive food SPT is higher in IBS patients than in controls.
© 2006 The WJG Press. All rights reserved.
Key words: Irritable bowel syndrome; Skin prick test; Food allergy
Jun DW, Lee OY, Yoon HJ, Lee SH, Lee HL, Choi HS, Yoon BC, Lee MH, Lee DH, Cho SH. Food intolerance and skin prick test in treated and untreated irritable bowel syndrome. World J Gastroenterol 2006; 12(15): 2382-2387
http://www.wjgnet.com/1007-9327/12/2382.asp
INTRODUCTION Irritable bowel syndrome (IBS) is common. Depending on the studies, the prevalence (using Rome II criteria) varies between 9% - 22% among Caucasians[1-3]. In Korea, the prevalence of IBS has been reported to be 6.6% and there is no difference in the prevalence between men and women[4]. In patients with IBS, postprandial worsening of symptoms as well as food-related reactions to one or more foods is very common[5]. In published data, speculation of an immunological reaction to foods in IBS has been reported[6,7]. Data from dietary elimination and food challenge studies support the role of diet in the pathogenesis of IBS[8-10]. This hypothesis is supported by the response to disodium cromoglycate in such patients[11,12]. Although well designed randomized controlled studies are scarce, milk, wheat, egg and foods high in salicylates or amines are consistently a problem among the studies[13,14]. Recently, Dainese et al[7] have indicated discrepancies between reported food intolerance and skin prick test (SPT) findings in IBS patients, suggesting that the SPT used to identify food sensitization mediated by the IgE mechanism is inappropriate. IBS is a heterogeneous disease having various symptoms and severity. So in our study, IBS patients were divided into treatment and untreated groups. Moreover, to clarify the possible role of food hypersensitivity in IBS, we used both common food and inhalant antigens. The results of SPT for food allergens were compared to the SPT for inhalant allergens. The aim of this study was to correlate the clinical features of treated and untreated IBS patients to the results of the skin prick test for food and inhalant allergens, total IgE level, and radio- allegro-sorbent test (RAST)
MATERIALS AND METHODS Subjects The study protocol was approved by the Institutional Review Board of the Hanyang University. Among the 480 medical students, 35 meeting the Rome II but not treated for IBS and 35 randomly selected healthy undergradua-te students were recruited in the study. After giving their informed consent, all volunteers underwent a physical exa-mination and laboratory screening (upper gastrointestinal endoscopy, colonoscopy, routine red and white blood cell count, and biochemical examinations). Subjects receiving any medication (antihistamines, steroids, H2 receptor antagonist, anti-inflammatory drugs, and herb medications) over a two-week period prior to study and those with current severe allergic disease identified by interview were excluded from the study (n = 9). Therefore, out of 70 students, 31 untreated IBS students and 30 healthy students participated in the trial. Forty-four consecutive patients with IBS referred to our institution for evaluation and treatment served as positive controls. Standard workup included upper gastrointestinal endoscopy, laboratory testing and colonoscopy. The enrolled patients were divided into three groups after clinical evaluation and the application of Rome II criteria. Group I consisted of 44 patients with IBS referred to our institution for evaluation and treatment. All treated patients were selected from a single tertiary outpatient clinic (treatment group). Group II consisted of 31 untreated IBS patients meeting the Rome Ⅱ criteria but not treated for IBS (untreated group). Group III consisted of 30 healthy undergraduate students (control group).
Questionnaire and clinical measurements
To assess abdominal symptoms and intensity, all study
participants were given a questionnaire. A modified WHOQOL (WHOQOL-BREEF)
method validated by Min
Skin prick test and RAST SPT was carried out on all subjects on the upper back involving the application of 70 fresh food extracts using the prick-by-prick method. Some of the fresh food extracts used were saury, mackerel, beef, pork, chicken, milk, egg white, egg yolk, wheat flour, buckwheat, rice, beans, apples, peaches, tomatoes, celery, carrots, onions, peanuts, chocolate, and coffee. A doctor carried out an additional SPT involving the application of inhalant allergens. The 11 commercial allergens tested for D-pteronyssinus, D-farinae, alternaria alternata, grass pollen, tree pollen, mugwort pollen, willow pollen, ragwort, dog hair, cat fur, and cockroaches mix. In both SPTs, one drop of the extract was placed on the skin, and a disposable syringe needle was placed into the drop and then into the skin until a small puncture was visible. A histamine control was employed. SPT was considered positive if the net wheal diameter was significantly greater than the net wheal diameter of the histamine reaction. The reaction to the extract was measured 15-20 min after application. Discomfort and bleeding were not evident. Serum samples for total IgE and total eosinophil count were collected by trained phlebotomists. Two 10 mL blood samples from an antecubital vein were taken. IgE measurement was determined by the paper radioimmunosorbent test (PRIST, Pharmacia Laboratories, USA) using a Phadebas IgE kit. The total IgE test provided evidence for IgE sensitivity to antigens because the IgE antibody resulted in mast cell activation and release of histamine. Also, total eosinophils were stained with a Hinkelman solution, and the eosinophil count provided immediate hypersensitivity to IgE antibody.
Statistical analysis Tables were constructed for frequency and percentage. Categorical data were analyzed using the chi-square test or Fisher's exact test. Continuous data were analyzed using the Student's t-test and one-way ANOVA or Scheffe's test. To minimize type I errors, P < 0.05 was considered statistically significant. Exact P-values are listed in the tables and text. All statistical analyses were performed using the SPSS 11.0 statistical package.
RESULTS Patient population In the study population, 44 treated IBS patients had a mean age of 38 years (37.9±13.2), 31 untreated IBS patients had a mean age of 27 years (27.2±1.9), and 30 controls had a mean age of 26 years (25.8±1.7). There were no statistically significant differences in gender ratio, height, weight, alcohol and coffee intake, and smoking habits among the three groups (not shown). In the treated group, the number of females (56.8%, n = 25) was greater than that of males (43.2%, n = 19). In this group, the most subtype IBS was found in 19 patients. The sub-type constipation dominant IBS was found in 12 patients of untreated group. Subjects in the treated group mainly sought for a primary care setting as the first visit due to abdominal pain (15 patients), stool pattern change (13 patients) and abdominal bloating (13 patients) (Table 1).
Subgroup analysis and scores of quality of life (WHOQOL-BREEF) We utilized a questionnaire to compare and estimate the onset, duration and severity of symptoms between the two IBS groups. More than half of the treated IBS patients (59.1%) reported that the symptoms lasted for more than 24 h, but only 29.0% of untreated IBS patients reported that the symptoms lasted for more than 24 h. Five IBS patients (11.4%) in the treated group complained of abdominal symptoms almost all day for more than one month. Subjective severity score of symptoms was also higher in the treated IBS patients than that of the untreated IBS patients (P = 0.001). But there was no significant difference in the onset of the disease between the two groups (P = 0.065) (Table 2). Modified WHOQOL (WHOQOL-BREEF) questionnaire validated by Min et al[15] was used. It consisted of 26 items measuring four dimensions of health. All dimensions including overall quality of life scores were significantly lower in IBS patients than in controls (Table 3).
History of allergies and food intolerance There was no significant difference in the reported food intolerance among the three groups. However, among the treated and untreated IBS patients, dairy products were reported to cause most of the intolerance. Of the treated and untreated IBS patients, 25 (56.8%) and 21 (67.7%) had an allergic condition and only 9 (30%) of the controls had an allergic condition (P = 0.008). However, no difference in the number of allergic conditions was found between the treated and untreated IBS patients. Rhinitis was the most common condition, and five patients had a history of asthma in the IBS patients (Table 4).
Skin prick test and IgE level Seventy fresh food extract allergens were used to identify the cause of food hypersensitivity. SPT results were different among the three groups. SPT was positive in 17 (38.6%) treated IBS patients, in 5 (16.1%) untreated IBS patients, and in 1 (3.3%) control (P < 0.01). The number of positive SPTs was greater in the IBS patients than in the controls (P < 0.001). The number of positive food SPTs was greater in the treated patients than in the untreated patients (P = 0.03). The most frequent SPT positive food allergen was saury among the different groups. Five IBS patients had positive SPT for rice (Table 5). Eleven treated and untreated IBS patients and four controls had positive SPT for inhalant allergens. No significant difference in SPT inhalant allergens was noted among the three groups. The most common reactive inhalant allergens were D-farinae and D-pteronyssinus. There were no significant differences in IgE and total eosinophil counts among the three groups. Also, no significant differences in IgE and total eosinophils were noted between the treated and untreated IBS patients (Table 6).
Characteristics according to the food SPT in treated and untreated groups When SPT for food allergen and gender ratio were compared between those with a positive and negative SPT, no difference was noted. Also, there were no significant differences in positive SPT between IBS subtype and current allergy history. However, food intolerance and positive inhalant allergen were much higher in SPT positive food allergens (P = 0.013, P = 0.006). Twenty-two IBS patients had one or more skin positive tests. Serum samples were taken for RAST in order to compare the SPT results. Only three treated IBS patients had a positive RAST for beans, pork, and beef (Table 7).
DISCUSSION The term “adverse food reaction” or “food-related symptoms” encompasses immunological responses and non-immunological responses to food. Food hypersensitivity/allergy is used to describe conditions in which an immunological mechanism may be demonstrable[16,17]. In contrast, food intolerance is a non-immunological response to proteins that may result from particular constituents of foods such as toxins (e.g., food poisoning) or pharmacological agents (e.g., caffeine or tyramine) or from host factors such as lactase deficiency. However, food hypersensitivity resulting in food intolerance in the cause of gastrointestinal problems is much harder. Niec et al[18] reported that milk, wheat, eggs, potatoes, and celery are the most commonly identified factors causing gastrointestinal symptoms. Locke et al[19] reported that beans and legumes, chocolate, dairy products, and nuts are the most common foods causing hypersensitivity. It was reported that patients with IBS reveal intolerance to foods such as milk, bread, pizza, apple, hazelnut, tomato, egg, peach, and greens[7]. In our study, dairy products, coffee, alcohol, raw food, and spicy food were the most common foods causing problems. However, SPT was positive for saury, rice, mackerel, buckwheat, sweet potatoes, celery, onions, and trumpet shell. The results of different studies are inconsistent, which poses the question of the population specificity of such studies. No correlation between SPT and patient’s intolerance to certain foods was noted. There are several explanations for the discrepancies between reported food intolerance and SPT results. First, SPT is generally considered the most convenient and least expensive screening method for detecting allergic reactions in most patients. However, until the diagnostic efficacy of SPT is fully established with standardized allergens and methods, a positive skin test alone cannot confirm a definite clinical sensitivity to an allergen. Second, clinicians consider cross-reactions among various plants and animal allergens[20, 21]. The conservation of these proteins across biologic substances affects cross-reactivity in several ways. Certain foods (e.g., peanut) are able to sensitize and elicit reactions after oral exposure (type 1 allergy) and can trigger responses to related foods (e.g. legumes). Other foods (e.g., apples) containing labile proteins are not strong oral sensitizers. Helbling et al[22] have reported the clinical cross-reactivity to most fish species and several in vitro studies have demonstrated the existence of common allergens between different fish species[23-26]. The third explanation is that food allergies are localized at the intestinal mucosa and specific IgEs are primarily present in intestinal mucosa but not systemically. For this reason, Andre et al[27] have indicated the importance of stool IgE rather than serum IgE. Bischoff et al[28] have also stressed the importance of stool eosinophil counts and mast cell mediators. Both SPT and RAST are for IgE-mediated disease, but there is no correlation between the two methods. However, RAST is not as sensitive as the skin test. As a result, in patients with a history of reactions to foods, insect stings, drugs, or latex, skin testing is still required because of its higher sensitivity even if the RAST is negative. The primary advantage of RAST over SPT is safety with the results not influenced by skin disease or medication[29].
In our study, the IBS patients showed much higher In this study, the untreated IBS patients were older than the treated patients (P = 0.005). Because age could affect SPT, it may confound our results. But the number and size of prick skin reactions increase throughout childhood until twenty years of age and then gradually decline until age fifty[32]. Even if age is considered, more treated patients were positive for SPT in our study. In conclusion, more IBS patients are positive for SPT and food allergens than healthy controls. However, the IBS patients present more severe symptoms, lower overall quality of life, and higher positive SPT compared to the untreated IBS patients even though the history of allergies is not different.
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