Double-blind Placebo-controlled Challenge Research Articles

A22 INVESTIGATING THE EFFECTS OF DIET TRIGGER DISCLOSURE ON BEHAVIOUR IN IRRITABLE BOWEL SYNDROME (IBS) PATIENTS WITH PERCEIVED GLUTEN SENSITIVITY

Abstract Background Patients with self-perceived gluten sensitivity often undergo double-blinded, placebo-controlled (DBPC) challenge studies to determine whether gluten or wheat trigger their symptoms. However, it is unknown whether the result disclosure impacts patients’ beliefs and dietary choices. Aims To evaluate the impact of disclosing results of DBPC challenge with gluten and wheat on beliefs and dietary choices in IBS patients who adopt a gluten-free diet (GFD). Methods We conducted a DBPC crossover trial in 28 adult IBS patients (Rome IV) who previously reported improvement of symptoms while on a GFD. Patients were on a GFD throughout the study and were challenged for 7 days with whole wheat, purified gluten, and nocebo (gluten-free flour) added to low-FODMAP cereal bars, followed by 2-week washouts. Genetic predisposition to celiac disease and anti-gliadin IgG (AGA) were assessed. At least 6 months after the study completion, patients were contacted to assess their current diet, dietary beliefs, and symptoms prior to disclosing their study results. We assessed the same outcomes one month later. Statistical comparisons used paired Wilcoxon signed rank tests. Results The DBPC study showed similar proportions of participants reacting to wheat, gluten, and nocebo challenge, with greater symptoms after wheat compared to baseline (P<0.05). AGA IgG were present in 8% (2/25) and celiac disease-related genes in 80% (20/25) of patients. Out of 28 participants, 26 completed the pre-disclosure and 25 completed post-disclosure follow-up. All participants (N=26) believed that at least one challenge triggered their symptoms: whole wheat N=22, pure gluten N=23, nocebo N=2. Prior to disclosure, 17 participants continued while 9 abandoned the GFD; none changed their diet post-disclosure. Reasons to stay on the GFD included belief in its efficacy (N=16) and better quality of life (N=15), while reasons for abandoning included difficulty to adhere to the GFD and its cost (N=6) and losing belief in its efficacy (N=3). IBS symptoms did not change pre- vs. post-disclosure. Participants not reacting to wheat or gluten challenge expressed slightly lower median belief in GFD efficacy pre- vs. post-disclosure (80%, IQR [64%, 97%] vs 71%, IQR [48%, 78%]; P=0.03; Figure 1). Those worsening after wheat or gluten did not change their beliefs. Conclusions Although most IBS patients with self-perceived gluten sensitivity had celiac disease predisposition, only some reacted to gluten or wheat. Furthermore, after disclosing the study results, all participants maintained their dietary habits avoiding gluten, thus suggestive of strong central mechanisms underlying their symptoms. Figure 1. Belief in GFD efficacy pre- vs. post-disclosure of study results. Funding Agencies CIHRSociety for the Study of Celiac Disease, Nestle

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test.

The aims of this observational “proof-of-concept” study were to analyze the clinical/psychological characteristics and gut microbiota/mycobiota composition of individuals with suspected non-celiac gluten/wheat sensitivity (NCGS/WS) according to responses to the double-blind-placebo-controlled (DBPC) crossover gluten challenge test. Fifty individuals with suspected NCGS/WS were subjected to the DBPC challenge test; anthropometric measurements, psychometric questionnaires, and fecal samples were collected. Twenty-seven (54%) participants were gluten responsive (NCGS), and 23 were placebo responsive, with an order effect. NCGS individuals displayed a significantly lower risk of eating disorders and a higher mental health score when compared to placebo-responsive participants, confirmed by multiple logistic regression analyses (OR = 0.87; 95% CI 0.76–0.98, p = 0.021, and OR = 1.30; 95% CI 1.06–1.59, p = 0.009, respectively). Principal coordinate analyses based on microbiota composition showed a separation by the DBPC response (p = 0.039). For Bacteroides (p = 0.05) and Parabacteroides (p = 0.007), the frequency of amplicon sequence variants was lower, and that for Blautia (p = 0.009) and Streptococcus (p = 0.004) was higher in NCGS individuals at multiple regression analyses. No difference in the mycobiota composition was detected between the groups. In conclusion, almost half of the individuals with suspected gluten sensitivity reported symptoms with placebo; they showed lower mental health scores, increased risk for eating disorders, and a different gut microbiota composition.

Successful introduction of milk after a negative double-blind placebo-controlled food challenge test is independent of the total dose and milk product used during the challenge test.

BackgroundFailure of milk introduction after a negative food challenge test is reported in a substantial number of patients. For this reason, guidelines recommend that the total dose of milk protein for a food challenge test should be comparable to a normal serving.ObjectiveOur aim is to compare the success rate of milk introduction after a negative double‐blind placebo‐controlled challenge test performed with different doses of milk protein and different milk products.MethodsWe conducted a retrospective chart review of 485 patients challenged with a low or high dose of milk protein. Pasteurized milk and milk protein powder were used for the low‐dose challenge tests, and condensed milk for the high‐dose challenge tests. Successful introduction was defined as regular milk consumption, and discontinuation of further introduction due to the reappearance of symptoms as unsuccessful introduction. We also evaluated the association between milk products and successful introduction.ResultsThe outcome of 288 (59.4%) double‐blind placebo‐controlled food challenge tests was negative. There were no significant differences between the low and high dose of milk protein in patient characteristics, percentage of patients lost to follow‐up (15% vs 20%), in whom introduction had not yet been performed (4% vs 3.1%), reappearance of symptoms (18% vs 17%), and successful introduction (88.0% and 83.4%). Age, gender, specific immunoglobulin E for milk, dose of milk protein, and atopy were not associated with successful introduction. Children who experienced symptoms during the introduction were less likely to consume milk (P < .001). There was a nonsignificant trend toward higher successful introduction rate if pasteurized milk was used as test material compared to milk protein powder, and condensed milk.Conclusion and Clinical RelevanceSuccessful introduction of milk after a negative challenge test is independent of the total dose of milk protein, and milk product used during the challenge test.

Abdominal Ultrasound Does Not Reveal Significant Alterations in Patients With Nonceliac Wheat Sensitivity.

The goal of this study was (A) to evaluate abdominal ultrasound signs in nonceliac wheat sensitivity (NCWS) patients for features useful in diagnosis and (B) to compare these aspects with those of celiac patients to assess whether ultrasound can be useful in the differential diagnosis between NCWS and celiac disease (CD). NCWS diagnosis is difficult as no biomarkers of this condition have as yet been identified. In CD ultrasound aspects have been identified that have a good diagnostic accuracy. We prospectively recruited 45 NCWS patients (11 males, 34 females; mean age 35.7 y). Three control groups were included: (A) 99 age-matched CD patients; (B) 18 patients with seronegative CD; (C) 50 patients with irritable bowel syndrome (IBS) who did not improve on a wheat-free diet. NCWS diagnosis was confirmed on the basis of an elimination diet and double-blind placebo-controlled (DBPC) challenge. Ultrasound sign investigation included: dilatation of the small bowel loops, thickening of the small bowel wall, hyperperistalsis, enlarged mesenteric lymph nodes, ascites, hyposplenism, altered diameter of the portal vein. NCWS patients showed a low frequency of pathologic ultrasound findings. Dilated or thickened loops appeared more often in CD patients than in NCWS patients (88.8% vs. 20%; P<0.0001). These US signs were significantly more frequent in seronegative CD than in NCWS patients (both P<0.0001), whereas no difference was found between NCWS patients and IBS controls. In NCWS patients' ultrasound does not show a characteristic pattern which could be helpful for diagnosis. However, US can be useful to differentiate between NCWS and CD patients and especially those with seronegative CD. (ClinicalTrials.gov NCT03017274).

The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge.

Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD). Twenty patients (14F/6M, age range: 21-62years) with suspected NCGS, without coeliac disease and wheat-allergy, were included while on a gluten-free diet. All patients went through four periods of double-blinded provocation, two with gluten and two with placebo in randomized order. They consumed two muffins a day (11/0g gluten) for 4days, followed by a 3-day wash-out. Gastrointestinal symptoms were recorded with questionnaires at baseline and after each provocation. We also investigated whether patients were able to correctly identify periods with gluten-exposure. Collectively the whole group reported the most severe symptoms after placebo (P=.012). Four out of twenty patients correctly identified the two periods when they received gluten, hence were diagnosed with NCGS. The diagnosed-group tended to show higher symptom scores than the not-diagnosed group both at baseline, after gluten exposure and after placebo, but no clear difference was seen between provocation with gluten and placebo. The not-diagnosed group showed more severe symptoms with placebo than with gluten (P=.029). The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms.

Component-resolved diagnostics demonstrates that most peanut-allergic individuals could potentially introduce tree nuts to their diet.

Nut allergy varies from pollen cross-allergy, to primary severe allergy with life-threatening symptoms. The screening of IgE antibodies to a wide spectrum of allergens, including species-specific and cross-reactive allergens, is made possible via microarray analysis. We sought to study the association of variable IgE sensitization profiles to clinical response in peanut-challenged children and adolescents in a birch-endemic region. In addition, we studied the avoidance of tree nuts and species-specific sensitizations. We studied 102 peanut-sensitized patients who underwent a double-blind placebo-controlled challenge to peanut. We analysed ISAC ImmunoCAP microarray to 112 allergens, singleplex ImmunoCAPs for hazelnut Cor a 14 and cashew Ana o 3, and performed skin prick tests to peanut, tree nuts and sesame seed. We surveyed avoidance diets with a questionnaire. Sensitization to PR-10 proteins was frequent (Bet v 1 90%), but equally high in the challenge negatives and positives. IgE to Ara h 2 and Ara h 6 discriminated peanut allergic (n=69) and tolerant (n=33) the best. Avoidance of tree nuts was common (52% to 96%), but only 6% to 44% presented species-specific sensitizations to tree nuts, so a great number could potentially introduce these species into their diet. PR-10-sensitizations were frequent and strong regardless of peanut allergy status. Component-resolved diagnostics can be employed to demonstrate to patients that sensitization to seed storage proteins of tree nuts is uncommon. Several tree nuts could potentially be reintroduced to the diet.

Conjunctival provocation test in diagnosis of peanut allergy in children.

Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy. To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy. This cross-sectional case-control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut-tolerant control group of 28 children of similar age was recruited locally. A double-blind placebo-controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double-blind placebo-controlled challenge in children with suspected peanut allergy and as an open challenge in the control children. All 81 children with a positive double-blind placebo-controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC. Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.

ContactDermatitisDuetoNickelAllergyinPatients SufferingfromNon-CeliacWheatSensitivity.

Background: Non-celiac wheat sensitivity (NCWS) is a new clinical entity in the world of gluten-related diseases. Nickel, the most frequent cause of contact allergy, can be found in wheat and results in systemic nickel allergy syndrome and mimics irritable bowel syndrome (IBS). Objective: To evaluate the frequency of contact dermatitis due to nickel allergy in NCWS patients diagnosed by a double-blind placebo-controlled (DBPC) challenge, and to identify the characteristics of NCWS patients with nickel allergy. Methods: We performed a prospective study of 60 patients (54 females, 6 males; mean age 34.1 ± 8.1 years) diagnosed with NCWS from December 2014 to November 2016; 80 age- and sex-matched subjects with functional gastrointestinal symptoms served as controls. Patients reporting contact dermatitis related to nickel-containing objects underwent nickel patch test (Clinicaltrials.gov registration number: NCT02750735). Results: Six out of sixty patients (10%) with NCWS suffered from contact dermatitis and nickel allergy and this frequency was statistically higher (p = 0.04) than observed in the control group (5%). The main clinical characteristic of NCWS patients with nickel allergy was a higher frequency of cutaneous symptoms after wheat ingestion compared to NCWS patients who did not suffer from nickel allergy (p < 0.0001). Conclusions: Contact dermatitis and nickel allergy are more frequent in NCWS patients than in subjects with functional gastrointestinal disorders; furthermore, these patients had a very high frequency of cutaneous manifestations after wheat ingestion. Nickel allergy should be evaluated in NCWS patients who have cutaneous manifestations after wheat ingestion.

Validation of Recipes for Double-Blind Placebo-Controlled Challenges With Milk, Egg White, and Hazelnut.

The double-blind, placebo-controlled food challenge (DBPCFC) is considered the definitive diagnostic test for food allergy. Nevertheless, validated recipes for masking the foods are scarce, have not been standardized, and differ between centers. Sensory evaluation techniques such as the triangle test are necessary to validate the recipes used for DBPCFC. We developed 3 recipes for use in DBPCFC with milk, egg white, and hazelnut and used the triangle test to validate them in a 2-phase study in which 197 volunteers participated. In each phase, participants tried 3 samples (2 active-1 placebo or 2 placebo-1 active) and had to identify the odd one. In phase 1, the 3 samples were given simultaneously, whereas in phase 2, the 3 samples of foods that failed validation in phase 1 were given sequentially. A visual analog scale (VAS) ranging from 1 to 10 was used to evaluate how much participants liked the recipes. In phase 1, the egg white recipe was validated (n=89 volunteers, 38.9% found the odd sample, P=.16). Milk and hazelnut recipes were validated in phase 2 (for both foods, n=30 participants, 36.7% found the odd sample, P=.36). Median VAS scores for the 3 recipes ranged from 6.6 to 9.7. We used sensory testing to validate milk, egg white, and hazelnut recipes for use in DBPCFC. The validated recipes are easy to prepare in a clinical setting, provide the equivalent of 1 serving dose, and were liked by most participants.

Suspected Nonceliac Gluten Sensitivity Confirmed in FewPatients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials.

A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered <8 g/d), and composition of the placebo (gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies.

Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet.

OBJECTIVES:Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS.METHODS:The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluorescence-activated cell sorting analysis for intracellular cytokines and surface markers.RESULTS:Rectal biopsies from wheat-challenged NCWS patients showed that a significant mucosal CD45+ infiltrate consisted of CD3+ and CD3− lymphocytes, with the latter spontaneously producing more interferon (IFN)-γ than IBS controls. About 30% of IFN-γ-producing CD45+ cells were T-bet+, CD56−, NKP44−, and CD117−, defining them as a type-1 innate lymphoid cells (ILC1). IFN-γ-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet.CONCLUSIONS:These data indicate that, in patients with active NCWS, IFN-γ-producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cell population in the pathogenesis of NCWS.

Reporte preliminar del abordaje diagnóstico de alergia alimentaria en pacientes con antecedente de dieta de eliminación

Food allergy diagnosis is performed by a double blind placebo controlled challenge; however, in a lot of patients, it is only based on clinical history, skin prick tests, or parents' perception. There is a high frequency of elimination diets without an adequate approach. To analyze the results of diagnostic tests in a group of children with elimination diet-based on suspected food allergy and verify such studies with double blind placebo-controlled test challenge. An observational, analytical and prospective study was done in a group of patients with elimination diet for suspected food allergy. We performed prick test, Prick-to-Prick test and patch test and the positive ones were verified by double-blind placebo-controlled challenge. Fourty-three patients were included within a total of 1,935 tests. Both approach for immediate and late sensitivity had not statistically significant relationship between a positive test and the elimination of food. Until now, we had 4 (8%) positive challenges out of 50. The frequency of allergy proved by double-blind placebo-controlled test in 50 challenges was of 8% (4/50), thus, in the preliminary report we found a high frequency of elimination diets without adequate support. It is very important that food allergy diagnosis is accurate and based on an appropriate approach; since the implementation of an elimination diet in pediatric population can have a negative influence on their growth and development.

Gluten Sensitivity in Pediatrics: A Clinical Conundrum

Non-celiac gluten sensitivity (NCGS) is a condition in which symptoms are triggered by gluten ingestion, in which both allergic and autoimmune mechanisms have been ruled out. The “classical” presentation of NCGS is a combination of gastrointestinal symptoms (including abdominal pain, bloating, and bowel habit abnormalities) and extra-intestinal manifestations. So far, NCGS has been described extensively in adults, and few data are available for the pediatric population. Due to lack of a serological or histological marker, the diagnosis of NCGS remains clinical and it is based on the exclusion of celiac disease and wheat allergy and on gluten challenge. G is a 2.5-year-old child referred to our Center for chronic diarrhea, diurnal abdominal pain, and mild failure to thrive. His mother reported that symptoms were related to wheat ingestion and that resolved on a gluten-free diet; therefore, she was worried about Celiac Disease. However, blood tests did support neither celiac disease because of anti-transglutaminase-IgA, anti-endomysium, and anti-gliadin-IgA negativity nor wheat allergy for the absence of specific IgE for wheat or gluten. G was positive just to anti-gliadin-IgG. We reassured the mother and concluded for a chronic unspecific diarrhea to be treated conservatively without elimination diets. On the follow-up visit, G was still complaining with same symptoms, and his growth was further slowing; we ,therefore, decided to repeat the blood tests (with similar results), to define the HLA status (DQ1/7), and to perform intestinal duodenal biopsies. These showed normal villous architecture and a modest increase of intraepithelial lymphocytes. Based on the clear association between clinical symptoms and wheat ingestion, the final diagnosis was “non IgE-mediated adverse reaction to wheat,” although G had no other clue to support this diagnosis such as personal or family history of atopy and/or eczema. G was started on a gluten-free diet with resolution of symptoms. This diagnosis was confirmed 6 months later with a double-blind placebo-controlled challenge that resulted in the onset of diarrhea and abdominal pain 30 h after wheat ingestion. This was happening in 2006 and 2 years later a “new” disease entity might have better explained the symptoms of this child: NCGS.

Skin Prick Test in the Diagnosis of Allergy in the Perioperative Period – 8 Year Experience

Epidemiological studies indicate an increase in allergies in the perioperative period. Some allergens can be lifethreatening. One of the most difficult and time-consuming issues in practical allergology is to diagnose the reactioninducing agent, particularly in the perioperative period. The paper presents various aspects of the diagnosis of allergy highlighting the usefulness of skin prick testing. The study involved 52 patients (42 women and 10 men). They were selected out of 72,380 patients anaesthetized for surgeries in 2003 and 2010. The physical examination of patients who experienced allergy determined the location, extent and severity of side effects. The tests were always conducted after inserting an intravenous catheter, under full safety conditions. A positive reaction after allergen application occurred in the form of a wheal of 3 mm or more in diameter and erythema. Patients were subjected to skin prick tests and intradermal tests using all anaesthetic drugs, including NMBAs, applied during anaesthesia (according to the anaesthesia protocol). Four patients (7.69 %) had positive SPT to latex, which showed clearly that it was the causative factor of the reaction. One of the patients (1.92 %) had positive SPT to atracurium, the others to augmentin and pethidine. Three patients (5.76%) had positive SPT to NMBA (atracurium, cisatracurium, rocuronium) (wheal size greater than 3 mm compared to the negative control). Positive intradermal test results to NMBA were identified in 27 patients (51.92 %). Patients received a written notice of the occurrence of suspected anaphylactic reaction during anaesthesia, the potential cause and the implemented therapeutic procedure. Increased dermographism made the skin tests in patients difficult to interpret, and therefore the following results were also taken into account: tryptase, specific IgE and clinical symptoms manifested during anaesthesia, recorded in patient records. Detailed history, skin prick testing, laboratory methods, and double-blind placebo-controlled challenges are still the gold standard for the diagnosis of hypersensitivity, although sometimes results can lead to difficulties of interpretation or can be even misleading.

Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg‐allergic children

Oral immunotherapy (OIT) is a promising treatment for food allergy but dose-related reactions are common. To evaluate safety of egg-OIT. To identify predictors of dose-related reactions. Fifty children aged 5-18 underwent egg-OIT after confirming IgE-mediated egg allergy by double-blind placebo-controlled challenge (DBPCFC). All dose-related reactions over a median period of 18 months on-OIT (range: 12-28) were registered. Children were retrospectively divided into three subgroups: (1) children who stopped reacting to OIT-doses over time (RR, Resolved Reactions); (2) children with ongoing dose-related reactions over the whole period on-OIT (PR, Persistent Reactions); (3) children who discontinued OIT within induction phase due to frequent reactions not improved by protocol re-adaptation and medication (ED, Early Discontinuation). Baseline clinical/immunological parameters associated with subgroups were investigated. Reactions occurred in 7.6% of doses. Adrenaline was required in 26% of children. The three subgroups corresponded to three different safety phenotypes: (1) twenty-four children (48%, RR) experienced infrequent and mainly mild reactions that resolved over time. None required adrenaline; (2) seventeen children (34%, PR) experienced more frequent and severe ongoing reactions over time; (3) nine children (18%, ED) discontinued OIT due to very frequent and mainly moderate reactions. Early discontinuation was associated with underlying asthma, higher specific IgE (sIgE) and lower threshold at DBPCFC. In contrast, lower sIgE and less severe reactions at DBPCFC were associated with subgroup RR. sIgE showed excellent performance in predicting belonging to subgroup RR. Levels below the optimal cut-off (ovomucoid-sIgE 8.85 kU/L) indicated 77% probability of belonging to subgroup RR, whereas levels above it indicated 95% probability of early discontinuation or ongoing reactions over time. Egg-OIT involves substantial risks. However, baseline parameters, particularly sIgE, may help identify children in whom the procedure is more likely to be safe. Egg-OIT safety needs improvement in children with more severe and persistent egg allergy.

Prevalence of Sensitivity to Food and Drug Additives in Patients With Chronic Idiopathic Urticaria

Chronic idiopathic urticaria (CIU) is defined as the presence of urticaria most days of the week for a period of 6 weeks or longer. There have been reports of food additive sensitivity in CIU previously, but the prevalence has not been precisely determined. To determine the prevalence of reactions to food and drug additives in patients with CIU. We challenged 100 patients in our allergy/immunology division with CIU to the 11 additives most commonly associated with reactions: tartrazine (FD&C Yellow 5), potassium metabisulfite, monosodium glutamate, aspartame, sodium benzoate, methyl paraben, butylated hydroxy anisole, butylated hydroxy toluene, FD&C Yellow 6, sodium nitrate, sodium nitrite. All of the patients had a history of CIU for longer than 6 weeks, and 43 reported possible history of food or drug additive sensitivity. Single-blind challenges to all of the additives were performed in the clinic and skin scores were recorded. Subjects with positive challenge tests underwent double-blind placebo controlled challenges. Of 100 subjects, only 2 had a positive urticarial response on single-blind challenge. Neither of these patients had a positive urticarial response on double-blind placebo-controlled challenge. There were no gastrointestinal, respiratory, or other symptom, and no patients reported late reactions. We were able to conclude, with 95% confidence intervals that sensitivity to any of the 11 food and drug additives occurs in fewer than 1% of patients with CIU. Food and drug additives appear to be a rare cause of CIU, and avoidance is not recommended.

The value of mucosal allergen challenge for the diagnosis of food allergy

The incidence of food allergy is increasing. Correct diagnosis is dependent on food challenges, which are not always performed, but more often based on history, skin prick test and specific IgE, leading to possible misdiagnoses. Mucosal provocation tests have been proposed as possible new diagnostic tools during recent decades. The databases EMBASE, PUBMED and Cochraine Review were used. Seven full text articles fulfilled criteria for mucosal challenge and food allergy, only one from the last 12 months. Conjunctival, nasal, buccal, gastric and coecal/rectal mucosa have been challenged. All authors find mucosal changes after challenge, but the lack of validation against double-blind placebo-controlled challenges makes evaluation difficult, with the exception of the conjunctival provocation test. As most mucosal surfaces are easily available, and small amounts of allergen are needed for an obvious reaction, this tool for diagnosing food allergy is promising. Further studies are however needed.

Oligo-Antigenic Diet in the Treatment of Chronic Anal Fissures. Evidence for a Relationship Between Food Hypersensitivity and Anal Fissures

Patients with chronic constipation due to food hypersensitivity (FH) had an elevated anal sphincter resting pressure. No studies have investigated a possible role of FH in anal fissures (AFs). We aimed to evaluate (1) the effectiveness of diet in curing AFs and to evaluate (2) the clinical effects of a double-blind placebo-controlled (DBPC) challenge, using cow's milk protein or wheat. One hundred and sixty-one patients with AFs were randomized to receive a "true-elimination diet" or a "sham-elimination diet" for 8 weeks; both groups also received topical nifedipine and lidocaine. Sixty patients who were cured with the "true-elimination diet" underwent DBPC challenge in which cow's milk and wheat were used. At the end of the study, 69% of the "true-diet group" and 45% of the "sham-diet group" showed complete healing of AFs (P<0.0002). Thirteen of the 60 patients had AF recurrence during the 2-week cow's milk DBPC challenge and 7 patients had AF recurrence on wheat challenge. At the end of the challenge, anal sphincter resting pressure significantly increased in the patients who showed AF reappearance (P<0.0001), compared with the baseline values. The patients who reacted to the challenges had a significantly higher number of eosinophils in the lamina propria and intraepithelial lymphocytes than those who did not react to the challenges. An oligo-antigenic diet combined with medical treatment improved the rate of chronic AF healing. In more than 20% of the patients receiving medical and dietary treatment, AFs recurred on DBPC food challenge.

Observations on the Paper of Carroccio et al. “Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity”

Villanacci, Vincenzo MD1; Lanzini, Alberto2; Lanzarotto, Francesco MD2; Ricci, Chiara MD2 Author Information

A comparison between two different in vitro basophil activation tests for gluten- and cow’s milk protein sensitivity in irritable bowel syndrome (IBS)-like patients

The diagnosis of food hypersensitivity (FH) in adult patients with gastrointestinal symptoms, beyond the immediate IgE-mediated clinical manifestations, is very often difficult. The aims of our study were to: 1) evaluate the frequency of FH in patients with irritable bowel syndrome (IBS)-like clinical presentation; and 2) compare the diagnostic accuracy of two different methods of in vitro basophil activation tests. Three hundred and five patients (235 females, age range 18-66 years) were included and underwent a diagnostic elimination diet and successive double-blind placebo-controlled (DBPC) challenges. Two different methods of in vitro basophil activation tests (BAT) (CD63 expression after in vitro wheat or cow's milk proteins stimulation) were evaluated: one was performed on separated leukocytes, and the other on whole blood. Ninety patients of the 305 studied (29.5%) were positive to the challenges and were diagnosed as suffering from FH. BAT on separate leukocytes showed a sensitivity of 86% and a specificity of 91% in FH diagnosis. BAT on whole blood showed a sensitivity of 15%-20% and a specificity of 73% in FH diagnosis (p<0.0001 compared to the other method). About one third of the IBS patients included in the study were suffering from FH and were cured on the elimination diet. The BAT based on CD63 detection on whole blood samples did not work in FH diagnosis and showed a significantly lower sensitivity, specificity and diagnostic accuracy than the assay based on separated leukocytes.