More children and even adults seem to be allergic to various foods these days than in the past. Also apparently on the rise is a linked condition, eosinophilic esophagitis.
The reason for these increases is not clear. This article confines itself to what we know about the mechanisms of food allergies and eosinophilic esophagitis, how to diagnose them, and how to treat them.
FOOD ALLERGIES ARE COMMON, AND MORE PREVALENT THAN EVER
Food allergies—abnormal immune responses to food proteins1—affect an estimated 6% to 8% of young children and 3% to 4% of adults in the United States,2,3 and their prevalence appears to be rising in developed countries. Studies in US and British children indicate that peanut allergy has doubled in the past decade. 4
Any food can provoke a reaction, but only a few foods account for most of the significant allergic reactions: cow’s milk, soy, wheat, eggs, peanuts, tree nuts, fish, and shellfish.
Approximately 80% of allergies to milk, egg, wheat, and soy resolve by the time the patient reaches early adolescence.6 Fewer cases resolve in children with tree nut allergies (approximately 9%) or peanut allergy (20%),7,8 and allergies to fish and shellfish often develop or persist in adulthood.
A family history of an atopic disease such as asthma, allergic rhinitis, eczema, or food allergy is a risk factor for developing a food allergy. 3 Considering that the rate of peanut allergy has doubled in children over the past 10 years, environmental factors may also play a role.3
How we tolerate foods or become allergic to them
The gut, the largest mucosal organ in the body, is exposed to large quantities of foreign proteins daily. Most protein is broken down by stomach acid and digestive enzymes into lessantigenic peptides or is bound by secretory immunoglobulin A (IgA), which prevents it from being absorbed. Further, the epithelial cells lining the gut do not allow large molecules to pass easily, having tight intracellular junctions and being covered with mucus.
For these reasons, less than 2% of the protein in food is absorbed in an allergenic form.9 The reason food allergies are more prevalent in children is most likely that children have an immature gut barrier, lower IgA levels, a higher gastric pH, and lower proteolytic enzyme levels.
When dietary proteins do cross the gut barrier, the immune system normally suppresses the allergic response. Regulatory T cells, dendritic cells, and local immune responses play critical roles in the development of tolerance. Several types of regulatory T cells, such as Tr1 cells (which secrete interleukin 10), TH3 cells (which secrete transforming growth factor beta), CD4+CD25+ regulatory T cells, gamma-delta T cells, and CD8+ suppressor cells can all contribute to suppressing allergic responses.10 Dendritic cells also help induce tolerance by stimulating CD4+ T cells to secrete transforming growth factor beta, which leads to the production of interleukin 10 and additional transforming growth factor beta.11
Factors that contribute to food allergy
Many factors may contribute to whether a person becomes tolerant to or sensitized to a specific food protein.
The dose of antigen. Tolerance can develop after either high or low doses of antigens, but by different mechanisms.
The antigen structure. Soluble antigens are less sensitizing than particulate antigens.12,13
Processing of foods. Dry-roasted peanuts are more allergenic than raw or boiled peanuts, partly because they are less soluble.13
The route of initial exposure. Sensitization to food proteins can occur directly through the gut or the skin. Alternatively, it can occur indirectly via the respiratory tract. Skin exposure may be especially sensitizing in children with atopic dermatitis.14,15
The gut flora. When mice are raised in a germ-free environment, they fail to develop normal tolerance.16 They are also more likely to become sensitized if they are treated with antibiotics or if they lack toll-like receptors that recognize bacterial lipopolysaccharides.17 Furthermore, human studies suggest that probiotics promote tolerance, especially in preventing atopic dermatitis, although the studies have had conflicting results.18–21
The gastric pH. Murine and human studies reveal that antacid medications increase the risk of food allergy.22,23
Genetic susceptibility. A child with a sibling who is allergic to peanuts is approximately 10 times more likely to be allergic to peanuts than predicted by the rate in the general population. Although no risk-conferring gene has been identified, a study of twins showed concordance for peanut allergy in 64.3% of identical twins vs 6.8% of fraternal twins.24