Irritable bowel syndrome (IBS) is one of the most common disorders managed by primary care physicians and gastroenterologists.1 Characterized by abdominal pain coinciding with altered stool form and/or frequency as defined by the Rome IV diagnostic criteria,2 symptoms range from mild to debilitating and may remarkably impair quality of life and work productivity.1
The cause of IBS is poorly understood. Proposed pathophysiologic factors include impaired mucosal function, microbial imbalance, visceral hypersensitivity, psychologic dysfunction, genetic factors, neurotransmitter imbalance, postinfectious gastroenteritis, inflammation, and food intolerance, any or all of which may lead to the development and maintenance of IBS symptoms.3 More recent observations of inflammation in the intestinal lining4,5 and proinflammatory peripherally circulating cytokines6 challenge its traditional classification as a functional disorder.
The cause of this inflammation is of intense interest, with speculation that the bacterial microbiota, bile acids, association with postinfectious gastroenteritis and inflammatory bowel disease cases, and/or foods may contribute. Although approximately 50% of individuals with IBS report that foods aggravate their symptoms,7 studies investigating type I antibody–mediated immediate hypersensitivity have largely failed to demonstrate a substantial link, prompting many authorities to regard these associations as food “intolerances” rather than true allergies. Based on this body of literature, a large 2010 consensus report on all aspects of food allergies advises against food allergy testing for IBS.8
In contrast, by utilizing type IV food allergen skin patch testing, 2 proof-of-concept studies9,10 investigated a different allergic mechanism in IBS, namely cell-mediated delayed-type hypersensitivity. Because many foods and food additives are known to cause allergic contact dermatitis,11 it was hypothesized that these foods may elicit a similar delayed-type hypersensitivity response in the intestinal lining in previously sensitized individuals. By following a patch test–guided food avoidance diet, a large subpopulation of patients with IBS experienced partial or complete IBS symptom relief.9,10 Our study further investigates a role for food-related delayed-type hypersensitivities in the pathogenesis of IBS.
Methods
Patient Selection
This study was conducted in a secondary care community-based setting. All patients were self-referred over an 18-month period ending in October 2019, had physician-diagnosed IBS, and/or met the Rome IV criteria for IBS and presented expressly for the food patch testing on a fee-for-service basis. Subtype of IBS was determined on presentation by the self-reported historically predominant symptom. Duration of IBS symptoms was self-reported and was rounded to the nearest year for purposes of data collection.
Exclusion criteria included pregnancy, known allergy to adhesive tape or any of the food allergens used in the study, severe skin rash, symptoms that had a known cause other than IBS, or active treatment with systemic immunosuppressive medications.
Patch Testing
Skin patch testing was initiated using an extensive panel of 117 type IV food allergens (eTable)11 identified in the literature,12 most of which utilized standard compounded formulations13 or were available from reputable patch test manufacturers (Brial Allergen GmbH; Chemotechnique Diagnostics). This panel was not approved by the US Food and Drug Administration. The freeze-dried vegetable formulations were taken from the 2018 report.9 Standard skin patch test procedure protocols12 were used, affixing the patches to the upper aspect of the back.