Non-celiac wheat sensitivity: a search for the pathogenesis of a self-reported condition

A significant percentage of the general population reports gastrointestinal and non-gastrointestinal symptoms caused by wheat and/or gluten ingestion, even though they do not suffer from celiac disease (CD) or wheat allergy (WS), because they test negative both for CD-specific serology and histopathology. All patients report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). The objective of this paper was to review some studies regarding the pathogenesis of NCGS to summarize the current hypotheses about the mechanisms, which can lead to NCGS. Particular attention was given to the immunologic and the malabsorptive hypotheses. We reviewed data of our previous studies involving patients diagnosed with NCWS by means of double-blind placebo-controlled wheat challenge. The data indicating a possible wheat allergy diagnosis were examined and other data in the literature were reviewed; we also reviewed the putative role of fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAPs) and of α-amylasetrypsin inhibitors (ATIs) proteins in the NCGS pathogenesis. NCGS pathogenesis has been attributed to very different mechanisms, among others: i) activation of innate and adaptive immunity (the immune/allergic mechanisms) induced by gluten or the non-gluten ATI family; ii) incomplete digestion and/or absorption of FODMAPs (the intolerance mechanisms); and iii) psychological effect.We suggest that NCGS is a heterogeneous condition, which includes different subgroups of patients who have different pathogenic mechanisms: strong data suggest a direct pathogenic immunogenic/inflammatory role of wheat-cereal proteins (not only gluten) in a subgroup, probably the largest, of these patients

Leukotriene receptor antagonists in monotherapy or in combination with antihistamines in the treatment of chronic urticaria: a systematic review

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST)]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis

Contact Dermatitis Due to Nickel Allergy in Patients Suffering from Non‐Celiac Wheat Sensitivity

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 gastrointestina l 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

Body Mass Index and Associated Clinical Variables in Patients with Non-Celiac Wheat Sensitivity

Background: Non-Celiac Wheat Sensitivity (NCWS) is still a largely undefined condition, due to the lack of a diagnostic marker. Few data are available about the nutritional characteristics of NCWS patients at diagnosis. Aims: To evaluate the proportion of NCWS patients who were underweight, normal weight, overweight, or obese at diagnosis, and to search for possible correlations between their Body Mass Index (BMI) and other NCWS-related disease characteristics. Patients and Methods: The clinical charts of 145 NCWS patients (125 F, 20 M, mean age 37.1 ± 11.4 years), diagnosed between January 2012 and March 2018, were reviewed. As a comparison, 84 celiac disease (CD) patients (73 F, 11 M, mean age 39.8 ± 13.9 years) were evaluated. All NCWS diagnoses were based on a double-blind placebo-controlled wheat challenge (DBPCWC) method. Results: BMI distribution was similar in the NCWS (6.2% underweight and 15.2% obese subjects) and CD patients (6% underweight and 7.1% obese subjects). Underweight NCWS subjects were significantly younger and had a shorter clinical history than the overweight or obese ones. Unlike the other NCWS patients, none of them had a DQ2 and/or DQ8 haplotype. Overweight and obese NCWS patients were more frequently suffering from associated autoimmune diseases than the other BMI categories (P = 0.05). Compared to the CD controls, NCWS patients showed a higher frequency of Irritable Bowel Syndrome (IBS)-like (P = 0.01) and extraintestinal symptoms (P = 0.03) and a longer clinical history (P = 0.04), whereas weight loss was more frequent in CD (P = 0.02). Conclusions: NCWS patients showed a BMI distribution similar to CD patients. However, NCWS was found to be a heterogenous condition that regards BMI, and clinical characteristics differed between the underweight and overweight/obese patients

Whole Cow’s Milk but Not Lactose Can Induce Symptoms in Patients with Self-Reported Milk Intolerance: Evidence of Cow’s Milk Sensitivity in Adults

Background: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. Methods: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 ± 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow’s milk challenge. Results: In the retrospective study, only 178 patients (56%) were lactose maldigesters and intolerant at LHBT; 68% of the subjects with SRMI were suffering from IBS; 74% reported dyspepsia (p = 0.0001 vs. IBS controls); and weight loss was recorded in 62 SRMI patients (20%) (p = 0.01 vs. IBS controls). Duodenal histology showed intra-epithelial lymphocytosis in about 60% of cases. In the prospective study, 36 patients (86%) experienced symptoms during the DBPC cow’s milk challenge, and only 4 patients (9%) reacted to placebo (p = 0.0001). Conclusions: A percentage of SRMI patients were not suffering from lactose intolerance. DBPC revealed that SRMI patients had clinical reactions when exposed to whole cow’s milk