Physicians are struggling to define and treat the growing population of patients who do not have celiac disease but who report improvement in GI symptoms when they eliminate wheat from their diet. Emotional factors, beliefs about diet, and patient expectations about GI symptoms interact here in clinically confusing ways. Many patients for whom we’ve ruled out celiac disease continue to report that wheat ingestion causes unpleasant symptoms of bloating, abdominal pain, and changes in stool consistency. Is this a placebo effect?
A rigorous Italian study in one of our premier gastroenterology specialty journals suggests that it is not; the study sheds light on wheat sensitivity (WS) as an emerging clinical entity.1 The study’s placebo controls for wheat intake helped sort out a possible connection between wheat ingestion and GI symptoms in non-celiac patients.
In a 10-year retrospective study, investigators reviewed all charts of adult patients in 2 outpatient gastroenterology specialty clinics who had presented with symptoms of irritable bowel syndrome (IBS). Patients were selected for study inclusion if they met established criteria for IBS but included evidence indicating the absence of celiac disease and wheat allergy, including all of the following:
• Negative serologies for anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) IgA antibodies
• Negative duodenal biopsy
• Negative IgE-mediated immuno-allergy tests to wheat (skin prick tests and serum-specific IgE—RASTs)
In addition, those chosen for inclusion underwent an elimination diet trial (wheat and dairy) with subsequent double-blind placebo-controlled (DBPC) challenge (with wheat and dairy sequestered into capsules, sequentially). Patients were excluded if they had IgA deficiency or already excluded wheat from their diet. There were 2 control groups: one contained 50 IBS patients without wheat or food sensitivity, and the other, 100 patients with a definitive diagnosis of celiac disease.
During the 10-year study period, 920 patients with IBS underwent an elimination diet trial with subsequent DBPC challenge (investigators used capsules containing wheat or placebo). Of these, 276 (30%) became asymptomatic on the elimination diet and showed symptoms again during DBPC challenge—nearly a third of patients classified as having IBS were actually wheat-sensitive when blindly challenged. Symptom scoring parameters included abdominal pain, bloating, and changes in stool consistency.
On the basis of symptom recurrence after DBPC challenge, pure WS was diagnosed in 70 patients (group 1), and multiple food sensitivities including wheat was diagnosed in 206 patients (group 2). None of the WS patients showed increased indexes of inflammation (C-reactive protein, erythrocyte sedimentation rate, or high white blood cell count) either before or after the challenges, but those with pure WS had higher rates of anemia (mostly iron deficiency) and weight loss than IBS control groups, and lower rates than celiac controls. By history, WS patients were more likely to have coexistent atopic diseases and food allergy in infancy. Group 2 patients (multiple food sensitivity) had a higher frequency of coexistent atopic disease. Both groups had eosinophil infiltration on biopsy, more so in group 2 (multiple food sensitivities).
In light of symptom recurrence following placebo-controlled challenge, the results suggest that WS is a true clinical entity worthy of further study, and that it is a heterogeneous condition with at least 2 distinct subtypes—one with pure WS more similar to celiac disease, and another with characteristics suggesting food allergy. How this will translate into clinical practice will be an evolving research area for the next several years, but clinicians should not expect gluten avoidance to disappear as yet another food fad.
1. Carroccio A, Mansueto P, Iacono G, et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012;107:1898-1906.
The American College of Gastroenterology has a useful discussion of this article as a free audio podcast at http://s3.gi.org/podcasts/DecemberPodcast.mp3