Clinical Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 21, 2006; 12(15): 2382-2387
Published online Apr 21, 2006. doi: 10.3748/wjg.v12.i15.2382
Food intolerance and skin prick test in treated and untreated irritable bowel syndrome
Dae-Won Jun, Oh-Young Lee, Ho-Joo Yoon, Seok-Hwa Lee, Hang-Lak Lee, Ho-Soon Choi, Byung-Chul Yoon, Min-Ho Lee, Dong-Hoo Lee, Sang-Hoen Cho
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.
Telephone: +82-2-22908343 Fax: +82-2-2298-9183
Received: July 23, 2005
Revised: October 9, 2005
Accepted: October 10, 2005
Published online: April 21, 2006


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.

Key Words: Irritable bowel syndrome, Skin prick test, Food allergy


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)


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 et al[15] was used to measure the quality of life in the IBS and control groups. The questionnaire consisted of 26 items measuring four dimensions of health: physical health, psychological health, social relationships and environmental health. Each item asked the respondents to indicate the extent to which their IBS interfered with their health during the previous four weeks.

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.

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).

Table 1 Characteristics of studied subjects, n (%).
(n = 44)(n = 31)(n = 30)
Age (years)37.9+13.227.2+1.925.8+1.7
Male19 (43.2)16 (51.6)22 (73.3)
Female25 (56.8)15 (48.4)8 (26.7)
IBS subgroups
C-IBS10 (22.7)12 (38.7)-
D-IBS15 (34.1)9 (29.0)-
A-IBS19 (43.2)10 (32.3)-
Type of initial health care system--
Tertiary center13 (29.5)--
Primary care25 (56.8)--
OB/Gyn 31 (2.3)--
Oriental-medicine5 (11.4)--
Reason for seeking for health care
Abdominal pain17 (38.7)--
Discomfort, bloating14 (31.8)--
Altered stool pattern13 (29.5)--
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).

Table 2 Symptoms, duration of symptoms, and onset of IBS, n (%).
(n =44)(n =31)
Duration of symptom0.035
Less than 1 h5 (11.4)7 (22.6)
1-24 h13 (29.5)15 (48.4)
More than 1 day26 (59.1)9 (29.0)
Severity of subjective symptoms0.001
Extremely severe6 (13.6)-
Very22 (50.0)5 (15.6)
Somewhat14 (31.8)19 (62.5)
Not very1 (2.3)6 (18.8)
Not at all severe1 (2.3)1 (3.1)
Onset of IBS symptoms0.065
Recent 6 mo3 (6.8)2 (6.3)
1 year ago8 (18.2)1 (3.1)
1-2 years ago6 (13.6)4 (12.5)
2-5 years ago13 (29.5)12 (40.6)
5-10 years ago7 (15.9)11 (34.4)
10-20 years ago5 (11.4)1 (3.1)
More than 20 years ago2 (4.5)-

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).

Table 3 Score of quality of life (mean ± SD).
DomainTreatedUntreatedControlPvalueaP valuec
(n =44)(n =31)(n = 30)
Physical health52.47±15.0659.09±13.1775.74±16.250.0010.001
Psychological health52.98±17.0056.06±13.7168.75±13.790.0010.014
Social relationships53.77±13.9259.47±11.5961.81±16.470.0670.005
Environmental health48.44±15.1954.69±11.1963.15±12.700.0010.005
Overall QOL5.79± 1.096.36± 1.338.21± 0.930.0010.002
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).

Table 4 History of allergies and food intolerance, n (%).
(n =44)(n =31)(n =30)value avalue cvalue e
History of allergies25 (56.8)21 (67.7)9 (30.0)0.017NS0.008
Atrophy5 (11.4)5 (16.1)2 (22.2)
Asthma3 (6.8)2 (6.5)-
Rhinitis10 (22.7)7 (22.6)5 (55.6)
Eczema4 (9.1)5 (16.1)3 (33.3)
Hives4 (9.1)7 (22.6)-
Reported food intolerance36 (81.8)27 (87.1)23 (76.7)NSNSNS
Dairy products24 (54.5)17 (54.8)11 (36.7)
Coffee13 (29.5)7 (22.6)6 (20.0)
Alcohol16 (36.4)15 (48.4)15 (50.0)
Cold, raw foods15 (34.1)10 (32.3)8 (26.7)
Spicy foods17 (38.6)6 (19.4)8 (26.7)
Others10 (22.7)3 (9.7)1 (3.3)
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.

Table 5 Skin prick test results using food allergens and inhalant allergens, n (%).
(n =44)(n =31)(n = 30)value avalue cvalue e
Positive food SPT17/44(38.6)5/31 (16.1)1/30 (3.3)<0.0010.03<0.001
Saury13 (76.5)2 (40.0)1 (100.0)
Mackerel3 (17.6)--
Beef1 (5.9)2 (40.0)-
Pork2 (11.8)1 (20.0)-
Buckwheat3 (17.6)--
Rice4 (23.5)1 (20.0)-
Arrowroot3 (17.6)--
Sweet potatoes3 (17.6)--
Beans2 (11.8)1 (20.0)-
Cabbages3 (17.6)--
Celery3 (17.6)--
Onions3 (17.6)--
Peach1 (5.9)1 (20.0)-
Tomato1 (5.9)--
Melon2 (11.8)--
Squid1 (5.9)1 (20.0)-
Trumpet shell3 (17.6)--
Curry2 (11.8)--
Positive inhalant SPT11 (25.0)11 (35.5)13.3 (4)NSNSNS
D-farinae7 (63.6)7 (63.6)50.0 (2)
D-pteronyssinus5 (45.5)8 (72.7)50.0 (2)
Alternaria alternate2 (18.2)-25.0 (1)
Grass pollen27.3 (3)1 (9.1)-
Tree pollen36.4 (4)1 (9.1)1 (25.0)
Mugwort pollen-2 (18.2)-
Willow pollen9.1 (1)--
Ragweed36.4 (4)3 (27.3)-
Dog hair45.5 (5)1 (9.1)1 (25.0)
Cat fur18.2 (2)--
Cockroach mix9.1 (1)--

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).

Table 6 IgE and total eosinophil count (mean ± SD).
TreatedUntreatedControlP value
(n =44)(n =31)(n = 30)
IgE (IU/mL)252.36 ± 558.94402.34 ± 765.00320.53 ± 659.07NS
Eosinophil (/μL)153.74 ± 149.68181.72 ± 126.04166.42 ± 139.10NS
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).

Table 7 Characteristics of treated and untreated patients with IBS, n (%).
CharacteristicsPositive food SPTNegative food SPTP value
(n =22)(n =53)
Male7 (31.8)28 (52.8)
Female15 (68.2)25 (47.2)
A-IBS8 (36.4)21 (39.6)
C-IBS9 (40.9)13 (24.5)
D-IBS5 (22.7)19 (35.8)
Current history of allergies13 (59.1)33 (62.3)NS
Reported food intolerance9 (40.9)7 (13.2)0.013
Inhalant positive SPT11 (50.0)11 (20.8)0.006
Positive RAST3 (13.6)-

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 positive SPT rates than the controls (P < 0.001). The treated IBS patients were more likely to have a positive SPT than the untreated IBS patients (P = 0.03). The untreated IBS patients defined by fulfillment of the Rome IBS criteria complained of severe symptoms (P < 0.05) (Table 2), suggesting a possible relationship exists between IBS and allergic diathesis. Further studies are needed to explore this relationship. In addition, we also used common inhalant allergens to compare with the food allergens and did not find any difference in positive SPT between inhalant allergens among the three groups (25%, 35% and 13% respectively). White et al[30] reported that increased airway responsiveness to inhaled methacholine can be demonstrated in irritable bowel syndrome patients with no clinical evidence for atopic disease[31]. These findings are in contrast to the previous hypothesis that IBS is a generalized immune hypersensitivity state. These findings also suggest that food allergens may play a certain role in IBS patients. However, well designed dietary elimination and food challenge studies are needed to document the food hypersensitivity in IBS patients.

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.


S- Editor Wang J L- Editor Wang XL E- Editor Ma WH

1.  Locke GR Jr. The epidemiology of functional gastrointestinal disorders in North America. Gastroenterol Clin North Am. 1996;25:1-19.  [PubMed]  [DOI]
2.  Talley NJ, Zinsmeister AR, Melton LJ Jr. Irritable bowel syndrome in a community: symptom subgroups, risk factors, and health care utilization. Am J Epidemiol. 1995;142:76-83.  [PubMed]  [DOI]
3.  Jones R, Lydeard S. Irritable bowel syndrome in the general population. BMJ. 1992;304:87-90.  [PubMed]  [DOI]
4.  Kim YJ, Ban DJ. Prevalence of irritable bowel syndrome, influence of lifestyle factors and bowel habits in Korean college students. Int J Nurs Stud. 2005;42:247-254.  [PubMed]  [DOI]
5.  Ragnarsson G, Bodemar G. Pain is temporally related to eating but not to defaecation in the irritable bowel syndrome (IBS). Patients' description of diarrhea, constipation and symptom variation during a prospective 6-week study. Eur J Gastroenterol Hepatol. 1998;10:415-421.  [PubMed]  [DOI]
6.  Soares RL, Figueiredo HN, Maneschy CP, Rocha VR, Santos JM. Correlation between symptoms of the irritable bowel syndrome and the response to the food extract skin prick test. Braz J Med Biol Res. 2004;37:659-662.  [PubMed]  [DOI]
7.  Dainese R, Galliani EA, De Lazzari F, Di Leo V, Naccarato R. Discrepancies between reported food intolerance and sensitization test findings in irritable bowel syndrome patients. Am J Gastroenterol. 1999;94:1892-1897.  [PubMed]  [DOI]
8.  Jones VA, McLaughlan P, Shorthouse M, Workman E, Hunter JO. Food intolerance: a major factor in the pathogenesis of irritable bowel syndrome. Lancet. 1982;2:1115-1117.  [PubMed]  [DOI]
9.  Bentley SJ, Pearson DJ, Rix KJ. Food hypersensitivity in irritable bowel syndrome. Lancet. 1983;2:295-297.  [PubMed]  [DOI]
10.  Farah DA, Calder I, Benson L, MacKenzie JF. Specific food intolerance: its place as a cause of gastrointestinal symptoms. Gut. 1985;26:164-168.  [PubMed]  [DOI]
11.  Stefanini GF, Prati E, Albini MC, Piccinini G, Capelli S, Castelli E, Mazzetti M, Gasbarrini G. Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type. Am J Gastroenterol. 1992;87:55-57.  [PubMed]  [DOI]
12.  Stefanini GF, Saggioro A, Alvisi V, Angelini G, Capurso L, di Lorenzo G, Dobrilla G, Dodero M, Galimberti M, Gasbarrini G. Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients. Scand J Gastroenterol. 1995;30:535-541.  [PubMed]  [DOI]
13.  Nanda R, James R, Smith H, Dudley CR, Jewell DP. Food intolerance and the irritable bowel syndrome. Gut. 1989;30:1099-1104.  [PubMed]  [DOI]
14.  Petitpierre M, Gumowski P, Girard JP. Irritable bowel syndrome and hypersensitivity to food. Ann Allergy. 1985;54:538-540.  [PubMed]  [DOI]
15.  Min SK, Lim KI, Park IH.  Korean version of WHOQOL. 1st ed, Seoul: Hana Publishing Co 2002; 5.  [PubMed]  [DOI]
16.  Anderson JA, Sogn DD. American Academy of Allergy and Immunology/NIAID. Adverse reactions to foods. NIH publication. 1984;1-6.  [PubMed]  [DOI]
17.  Bindslev-Jensen C, Ballmer-Weber BK, Bengtsson U, Blanco C, Ebner C, Hourihane J, Knulst AC, Moneret-Vautrin DA, Nekam K, Niggemann B. Standardization of food challenges in patients with immediate reactions to foods--position paper from the European Academy of Allergology and Clinical Immunology. Allergy. 2004;59:690-697.  [PubMed]  [DOI]
18.  Niec AM, Frankum B, Talley NJ. Are adverse food reactions linked to irritable bowel syndrome. Am J Gastroenterol. 1998;93:2184-2190.  [PubMed]  [DOI]
19.  Locke GR 3rd, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ. Risk factors for irritable bowel syndrome: role of analgesics and food sensitivities. Am J Gastroenterol. 2000;95:157-165.  [PubMed]  [DOI]
20.  Breiteneder H, Ebner C. Molecular and biochemical classification of plant-derived food allergens. J Allergy Clin Immunol. 2000;106:27-36.  [PubMed]  [DOI]
21.  Helbling A, McCants ML, Musmand JJ, Schwartz HJ, Lehrer SB. Immunopathogenesis of fish allergy: identification of fish-allergic adults by skin test and radioallergosorbent test. Ann Allergy Asthma Immunol. 1996;77:48-54.  [PubMed]  [DOI]
22.  de Martino M, Novembre E, Galli L, de Marco A, Botarelli P, Marano E, Vierucci A. Allergy to different fish species in cod-allergic children: in vivo and in vitro studies. J Allergy Clin Immunol. 1990;86:909-914.  [PubMed]  [DOI]
23.  Pascual C, Martín Esteban M, Crespo JF. Fish allergy: evaluation of the importance of cross-reactivity. J Pediatr. 1992;121:S29-S34.  [PubMed]  [DOI]
24.  Tuft L, Blumstein GI. Pollen tolerance nasal tests in hay fever experimental and clinical observations. J Allergy. 1950;21:326-333.  [PubMed]  [DOI]
25.  Clarke DJ, Burchell B, George SG. Differential expression and induction of UDP-glucuronosyltransferase isoforms in hepatic and extrahepatic tissues of a fish, Pleuronectes platessa: immunochemical and functional characterization. Toxicol Appl Pharmacol. 1992;115:130-136.  [PubMed]  [DOI]
26.  André F, André C, Colin L, Cavagna S. IgE in stools as indicator of food sensitization. Allergy. 1995;50:328-333.  [PubMed]  [DOI]
27.  Sampson HA, Ho DG. Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. J Allergy Clin Immunol. 1997;100:444-451.  [PubMed]  [DOI]
28.  Bischoff SC. Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut. Baillieres Clin Gastroenterol. 1996;10:443-459.  [PubMed]  [DOI]
29.  Ownby DR. Skin tests in comparison with other diagnostic methods. Immunol Allergy Clin North Am. 2001;21:355-367.  [PubMed]  [DOI]
30.  White AM, Stevens WH, Upton AR, O'Byrne PM, Collins SM. Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome. Gastroenterology. 1991;100:68-74.  [PubMed]  [DOI]
31.  Stefanini GF, Bazzocchi G, Prati E, Lanfranchi GA, Gasbarrini G. Efficacy of oral disodium cromoglycate in patients with irritable bowel syndrome and positive skin prick tests to foods. Lancet. 1986;1:207-208.  [PubMed]  [DOI]
32.  Barbee RA, Brown WG, Kaltenborn W, Halonen M. Allergen skin-test reactivity in a community population sample: correlation with age, histamine skin reactions and total serum immunoglobulin E. J Allergy Clin Immunol. 1981;68:15-19.  [PubMed]  [DOI]