“An Allergic Basis for Abdominal Pain”

A recent post (Mechanisms of Postinfectious IBS & Functional Pain) reviewed a study which described how food antigens during an infectious process can result in meal-induced pain.

A recent review of this study (M Rothenberg. NEJM 2021; 384:2156-2158. An Allergic Basis for Abdominal Pain) provides more insight.

Key points:

  • “A peripheral immune mechanism involving local mast cells stimulated by food-induced local IgE may underlie the symptoms associated with IBS and functional abdominal pain; these findings prompt consideration of new therapeutic strategies to target mast cells and allergies.”
  • The article reviews the experimental methods/results used in both mice and humans. Mice that were treated with agents that interfered with allergy “including anti-IgE, mast-cell stabilizers, and histamine H1 receptor antagonists, attenuated the pathologic and symptomatic responses…mice [that were] deficient in mast cells or in histamine H1 receptor were protected” as well.
  • The study shows that a “bacterial infection can break oral tolerance to a dietary antigen…which in turn can lead to increased gut permeability.”
  • The findings in human “showed no evidence of systemic IgE against common foods” but localized reactions were identified in every IBS patient after allergen injection into rectal mucosa.

My take: This study adds to the evidence that specific foods can lead to localized tissue-specific allergic responses. Nevetheless, it is still a futile effort to look for systemic allergic food reactions in patients with IBS and functional GI disorders.

Related blog posts:

Lots of Allergy & Autoimmunity Issues Following Solid Organ Transplantation

A recent retrospective cross-sectional cohort study (N Marcus et al. J Pediatr 2018; 196: 154-60, editorial page 10) identified 273 transplant recipients with a median followup of 3.6 years. This cohort included 111 liver transplant recipients, 103 heart transplant recipients, 52 kidney transplant recipients, and 7 multivisceral transplant recipients.

Key findings:

  • 92 (34%) developed allergy or autoimmunity after transplantation.
  • Allergic problems included eczema (n=44), food allergy (n=22), eosinophilic gastrointestinal disease (n=11), and asthma (n=28)
  • Autoimmunity problems developed in 6.6% (18) including autoimmune cytopenias (n=10). Two patients died due to autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis.
  • Allergic problems typically developed during the first year after transplantation and rarely after 5 years following transplantation.
  • ~20% required a change in immunosuppression
  • ~50% improved with time

In the editorial, the Dr. Helen Evans notes that the increasing reporting of atopic/allergic disorders could be due to recognition but could also be due, in part, to the widespread adoption of tacrolimus instead of cyclosporine for immunosuppression.

My take: Many have said that organ transplantation, which is life-saving, substitutes one problem for another.  This is an example of an additional burden, often related to immunosuppression, that patients and families have to manage afterwards.

Chattahoochee River, Island Ford

The “EAT” Study

A recent study from MR Perkin et al (NEJM 2016; 374: 1733-43) examined whether early introduction (3 months) of allergenic foods in 1303 infants lowered the rate of allergies to these foods at 3 years of life compared to standard introduction (after 6 months).  The six foods: peanut, egg, cow’s milk, sesame, whitefish, and wheat.

This EAT study (“Enquiring about Tolerance”) required parents in the intervention group to give 3 rounded teaspoons of smooth peanut butter, one small egg, two portions (40-60 g) of cow’s milk yogurt, 3 teaspoons of sesame paste, 24 g of white fish, and two wheat-based cereal biscuits every week.

While the study did not reach a statistical significance, the absolute rate of allergies was modestly lower in those in the early introduction group (5.6% compared with 7.1%).  In a per-protocol analysis of those who strictly adhered to the assigned treatment regimen, there was an even lower rate of 2.4% (compared to 7.3% in the standard group).  The associated editorial (pg 1783-84) indicates that the demanding protocol limited those who adhered to the protocol and points out that those who were not adherent could have been due to reverse causation (eg. subtle avoidance to certain foods due to reactions).  The editorial conclusion: “evidence is building that early consumption rather than delayed introduction of foods is likely to be more beneficial as a strategy for the primary prevention of food allergy.”

My take: Early introduction of allergenic solids at ~3 months of age probably lowers the risk of developing allergies to these foods.

Here’s a link to <2 minute quick take summary: The EAT Study NEJM

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Reference on consensus for guidance on introducing peanuts:  J Allergy Clin Immunol 2015; 136: 258-61.

Related blog posts:

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Only in Kids: Allergies Vary by Region

From the NIH:  link to full article: http://t.co/QuVzGFPTDb

An excerpt (highlighted for emphasis):

In the largest, most comprehensive, nationwide study to  examine the prevalence of allergies from early childhood to old age, scientists  from the National Institutes of Health report that allergy prevalence is the  same across different regions of the United States, except in children 5 years  and younger.

“Before this study, if you would have asked 10 allergy  specialists if allergy prevalence varied depending on where people live, all 10 of them would have said yes, because allergen  exposures tend to be more common in certain regions of the U.S.,” said Darryl  Zeldin, M.D., scientific director of the National Institute of Environmental  Health Sciences (NIEHS), part of NIH. “This study suggests that people prone to  developing allergies are going to develop an allergy to whatever is in their  environment. It’s what people become allergic to that differs.”

The research appeared online in February in the Journal of  Allergy and Clinical Immunology, and is the result of analyses performed on  blood serum data compiled from approximately 10,000 Americans in the National  Health and Nutrition Examination Survey (NHANES) 2005-2006.

… Among children  aged 1-5, those from the southern U.S. displayed a higher prevalence of  allergies than their peers living in other U.S. regions. ..

“The higher allergy prevalence among the youngest children  in southern states seemed to be attributable to dust mites and cockroaches,”  explained Paivi Salo, Ph.D., an epidemiologist in Zeldin’s research group and  lead author on the paper. “As children get older, both indoor and outdoor  allergies become more common, and the difference in the overall prevalence of  allergies fades away.”

The NHANES 2005-2006 not only tested a greater number of  allergens across a wider age range than prior NHANES studies, but also provided  quantitative information on the extent of allergic sensitization. The survey  analyzed serum for nine different antibodies in children aged 1-5, and nineteen  different antibodies in subjects 6 years and older. Previous NHANES studies used skin prick tests to test for allergies.

The scientists determined risk factors that made a person  more likely to be allergic. The study found that in the 6 years and older  group, males, non-Hispanic blacks, and those who avoided pets had an increased  chance of having allergen-specific IgE antibodies, the common hallmark of  allergies.

Socioeconomic status (SES) did not predict allergies, but  people in higher SES groups were more commonly allergic to dogs and cats,  whereas those in lower SES groups were more commonly allergic to shrimp and  cockroaches.