Evan Newnham

Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial

OBJECTIVES:Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism.METHODS:A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored.RESULTS:A total of 34 patients (aged 29–59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8.CONCLUSIONS:“Non-celiac gluten intolerance” may exist, but no clues to the mechanism were elucidated.

Review article: fructose malabsorption and the bigger picture.

Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine.

Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity.

Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance.

Quantifying exposure to diagnostic medical radiation in patients with inflammatory bowel disease: are we contributing to malignancy?

Background  While potential risks of diagnostic medical radiation are acknowledged, actual exposure of patients in routine clinical practice is poorly documented.

Cognitive impairment in coeliac disease improves on a gluten‐free diet and correlates with histological and serological indices of disease severity

Mild impairments of cognition or ‘Brain fog’ are often reported by patients with coeliac disease but the nature of these impairments has not been systematically investigated.

Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A 5-year longitudinal study from diagnosis.

Key aims of treatment of coeliac disease are to heal the intestinal mucosa and correct nutritional abnormalities.

Does gluten cause gastrointestinal symptoms in subjects without coeliac disease

Aim:  To determine the evidence for the effect of gluten ingestion on gastrointestinal symptoms, intestinal permeability and other indices of small intestinal injury in non‐coeliac, gluten intolerant individuals.

Safety of iron polymaltose given as a total dose iron infusion

An audit of the in‐hospital safety and tolerability of 401 infusions of iron polymaltose in 386 patients has shown no cases of anaphylaxis or other cardiorespiratory compromise. The infusion was terminated prematurely because of adverse events in six patients (1.6%). No adverse events occurred within the first 15 min of the infusion. Premedication (in 24%) was not associated with fewer adverse events. Fear of anaphylaxis should not inhibit the use of total dose iron infusion and the practices of premedication and of medical supervision during the first 15 min of the infusion should be abandoned.

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work‐up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence‐based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results.

Thiopurines, a previously unrecognised cause for fatigue in patients with inflammatory bowel disease ☆

BACKGROUND Active inflammatory bowel disease, anaemia, iron deficiency and depression, alone or in combination, are known contributing factors of fatigue in inflammatory bowel disease. However, in some patients, fatigue cannot be attributed to known causes. Thiopurines are not a recognized cause. AIM To describe the clinical scenario of a series of patients where thiopurines were the likely cause of fatigue. METHOD The clinical scenario of 5 patients was examined with specific reference to the temporal association of thiopurine therapy with fatigue, the effect of its withdrawal and rechallenge, and drug specificity. RESULTS The onset of severe fatigue was related to the introduction of azathioprine or 6-mercaptopurine, rapid relief was experienced on its withdrawal in all patients, and fatigue rapidly occurred on rechallenge. The speed of onset was rapid in two patients and in the context of gradual withdrawal of moderate steroid dose, but recurred rapidly on rechallenge when not on steroids. CONCLUSIONS Marked fatigue is a previously unrecognized adverse effect of thiopurines. It does not appear to be drug-specific. Its onset might be masked by concurrent steroid therapy.