Irritable bowel syndrome is a functional disorder of the gastrointestinal tract diagnosed with the Rome criteria. The Rome IV criteria are based on abdominal pain symptoms and stool habits including stool frequency and stool forms [1]. They define 3 main subtypes based on symptoms: 1) IBS with diarrhea; 2) IBS with constipation: and 3) mixed symptoms of constipation and diarrhea. The IBS with diarrhea (IBS-D) subtype has the highest prevalence. Currently, treatment of IBS-D includes antidiarrheals, bile acid sequestrants, antispasmodics, tricyclic antidepressants, and FODMAP diet. However, many patients are intolerant or unresponsive to the above treatments. Outside of IBS, chronic diarrhea affects about 5% of adults. We have described a syndrome in a subset of IBS patients presenting with post prandial diarrhea, flushing and dermatographia whose symptoms are prevented by pre-treatment with combined H1 and H2 antihistamines [2]. However, the prevalence of this syndrome among the IBS + D patients is not known nor have the clinical characteristics or predictors of antihistamine responsive IBS + D been defined.

We have published a series of 5 patients with chronic post prandial diarrhea (PPD) that begins within 3 hours after eating, associated with dermatographia, responsive to antihistamines [2]. In these cases, no underlying causes were identified to explain PPD; diagnoses of food allergy, lactose intolerance, celiac disease, dumping syndromes, inflammatory bowel disease, systemic mastocytosis were excluded. Patients with the syndrome have prior histories of chronic urticaria and experience associated transient symptoms of flushing, headache, tachycardia, and abdominal bloating during PPD episodes.

This syndrome, except for our published report, have not been previously described in the medical literature. Patients with systemic mastocytosis and mast cell activation syndrome experience PPD but along with anaphylactic manifestations (e.g. wheezing, hypotension) and measurable mast cell biomarkers are identifiable in affected patients (i.e. serum mast cell tryptase or 24 hour urine methylhistamine, PGF2a). Therefore, it is important to characterize PPD responsive to antihistamines in a general GI patient population and to publish our findings. The impact on human health will be substantial; we found that these patients are undiagnosed and untreated for many years.

Our aim is to recruit 50-100 patients from the UC Health affiliated gastroenterology clinics with access UC health which has 300-500 potential subjects. We would need to recruit 10-20% percentage of these potential subjects. Kris Ramprasad MD, a faculty member in the Division of Gastroenterology, David Bernstein MD, a faculty member in the Division of Allergy and Rheumatology, allergy fellows and GI fellows will direct and implement subject screening and consenting.

Inclusion Criteria:

• Age 18 years and older
• Prior to Diagnosis of IBS + diarrhea based on ICD 10 codes with or without constipation unresponsive to prior treatments
• Moderate to severe symptom severity score (>175 points) based on IBS symptom severity scale
• Seeking evaluation by a health care professional
• Negative serologic celiac panel
• No response to lactose elimination diet by history
• Normal colonoscopy
• Able to complete symptoms diaries and global evaluations

Exclusion Criteria:

• Confirmed IgE dependent food allergy as a cause of the gastrointestinal symptoms.
• Lactose intolerance by history
• Celiac disease by serology
• Inflammatory bowel disease or colitis
• Bile acid diarrhea by history
• Post-surgical GI symptoms (e.g., dumping syndrome) by history
• No colonoscopy performed
• GI malabsorption
• Current pregnancy
• Current severe depression or history of psychosis
• Current treatment with tricyclic antidepressants

This is a patient population of adults with chronic diarrhea that has been evaluated for the common causes and resulting with a diagnosis of exclusion: irritable bowel syndrome with diarrhea.

We do not plan on sharing individual participant data.