Antihistamines May Help Some Patients With Chronic Diarrhea

Nicola M. Parry, DVM

July 24, 2019

Some patients with idiopathic postprandial diarrhea (PPD) may respond to antihistamine treatment, according to a recent case series published online in Annals of Allergy, Asthma & Immunology.

"Antihistamine-responsive PPD is seen in patients with chronic idiopathic urticaria and/or dermatographia and can be distinguished from mast cell activation syndrome (MCAS)," write Yasmin Hassoun, MD, University of Cincinnati, Ohio, and colleagues.

"This syndrome should also be considered in the differential diagnosis of patients presenting with food intolerance after excluding food allergy and other gastrointestinal (GI) disorders."

Chronic diarrhea is a common problem that affects up to 5% of adults, and PPD comprises a subset of this condition.

The authors report the occurrence of idiopathic PPD in five patients aged 26 to 63 years with a diarrhea duration of 8 weeks to 13 years. All five patients had concurrent dermatographia. Three patients (two women and one man) also had a current or previous history of chronic urticaria, and three women had a current or previous history of angioedema.

None of the patients had experienced an initial triggering event such as viral illness.

In all five cases, diarrhea occurred only after meals or snacks, and within 3 hours of eating.

However, none of the patients showed any evidence of food allergy or food intolerance. Serum from four of the five patients was screened for food-specific IgE and tested negative. Three of the patients also undertook a lactose-free diet and other elimination diets without any improvement in symptoms.

Additional tests were performed in some cases, including anti-tissue transglutaminase IgA (in four patients) to rule out celiac disease, serum tryptase (in four patients), 24-hour urinary prostaglandin F (in three patients), and 24-hour urinary N-methylhistamine (in two patients) to investigate the possibility of MCAS. All of these tests were normal.

Four of the patients also underwent upper endoscopy and colonoscopy. Lesions were found in only two of these patients. One 55-year-old woman had lymphocytic colitis and a 63-year-old woman had gastric inflammation and ulcers. However, these findings could not account for an underlying GI disorder to explain their diarrhea.

After eliminating underlying food allergy or intolerance, GI disease, or MCAS as the cause of PPD, all five patients received daily pretreatment with H1 and H2 antihistamines.

This treatment resolved the PPD for two patients and alleviated it for the remaining three.

"The beneficial responses in these patients to H1 and H2 receptor blockers suggest that histamine released by GI mast cells is a key mediator of postprandial diarrhea," Hassoun and colleagues write.

Although the exact mechanism by which food stimulates GI mast cells is unknown, they hypothesize that peristalsis could play a role in activating mast cells.

David I. Bernstein, MD, also from the University of Cincinnati, told Medscape Medical News that he would expect most patients with idiopathic PPD and concurrent chronic idiopathic urticaria and/or dermatographia to respond to this type of antihistamine therapy.

"But there are variable degrees of response, from 60% to 100% control of GI symptoms," he emphasized. 

Although it is unknown how often this subset of patients visits allergy or gastroenterology clinics, Bernstein's group is now planning studies to determine this.

These are "interesting single-case observations with benefit from combination treatment with H1 and H2 blockers," said Michael Camilleri, MD, professor of medicine, pharmacology, and physiology at the Mayo Clinic in Rochester, Minnesota, in an interview with Medscape Medical News. 

The authors' statement that "the physiologic role of mast cells in the GI tract has not been clearly defined" is appropriate, he noted. "This association may be most relevant, as suggested, in patients with chronic urticaria or angioedema," he added.

According to Camilleri, histamine H1 receptors have also been shown to be involved in the modulation of pain sensation in patients with irritable bowel syndrome (IBS). In a recent study, the histamine H1 receptor antagonist ebastine reduced visceral hypersensitivity, symptoms, and abdominal pain in patients with IBS.

These interesting clinical observations in PPD require further study in randomized, placebo-controlled trials, he said. Additional studies might "include evaluation of the prevalence and natural history of this PPD and of optimal treatment regimens."

The authors and interviewees have reported no relevant financial relationships.

Ann Allergy Asthma Immunol. Published online July 3, 2019. Abstract

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