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In the past few decades, the indoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism has been the subject of much research in the area of immune tolerance. In this review, we aim to incorporate new findings on this pathway in relation to allergy and the gut microbiome, while providing a comprehensive overview of the pathway itself. Stimulated by interferon gamma, IDO acts as a tolerogenic, immunosuppressive enzyme to attenuate allergic responses by the induction of the KYN-IDO pathway, resultant depletion of TRP, and elevation in KYN metabolites. Acting through the aryl hydrocarbon receptor, KYN metabolites cause T-cell anergy and apoptosis, proliferation of Treg and Th17 cells, and deviation of the Th1/Th2 response, although the outcome is highly dependent on the microenvironment. Moreover, new evidence from germ-free mice and human infants shows that gut microbiota and breast milk are key in determining the functioning of the KYN-IDO pathway. As such, we recommend further research on how this pathway may be a critical link between the microbiome and development of allergy.

Background: The Cross-Canada Anaphylaxis Registry (C-CARE) assesses the triggers and management of anaphylaxis and identifies predictors of the development of severe allergic reactions and of epinephrine use. Here, we present data from an urban adult tertiary care emergency department (ED) in Montreal, Canada. Methods: Potential anaphylaxis cases were identified using ICD-10 codes related to anaphylaxis or allergic reactions. Putative cases underwent chart review to ensure they met anaphylaxis diagnostic criteria. Demographic, clinical and management data were collected. Multivariate logistic regressions were conducted to assess the effect of demographic characteristics, triggers, and comorbidities on severity and management of reactions. Results: Among 37,730 ED visits, 0.26% (95% CI 0.21, 0.32) fulfilled the definition of anaphylaxis. Food was the suspected trigger in almost 60% of cases. Epinephrine was not administered in almost half of moderate-to-severe cases, and similar numbers of individuals with moderate-to-severe reactions were not prescribed an epinephrine autoinjector. Reaction to shellfish was associated with more severe reactions (OR 13.9; 95% CI 2.2, 89.4). Older individuals and those not receiving steroids were more likely managed without epinephrine (OR 1.04; 95% CI 1.01, 1.07 and OR 2.97; 95% CI 1.05, 8.39, respectively). Conclusions: Anaphylaxis accounted for a substantial number of ED visits in adults, and the most common trigger was food. There is non-adherence to guidelines recommending epinephrine use for all cases of anaphylaxis. We postulate that this may be related to concerns regarding the side effects of epinephrine in adults.

Sesame is an important global allergen affecting ~0.1% of the North American population. It is a major cause of anaphylaxis in the Middle East and is the third most common food allergen in Israel. We conducted a systematic review of original articles published in the last 10 years regarding the diagnosis and management of sesame allergy. Skin prick testing appears to be a useful predictor of sesame allergy in infants, although data are less consistent in older children and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor, especially in studies that used oral food challenges to confirm the diagnosis. Double-blind, placebo-controlled food challenge thus remains the diagnostic gold standard for sesame allergy. The cornerstone of sesame allergy management is allergen avoidance, though accidental exposures are common and patients must be prepared to treat the consequent reactions with epinephrine. Novel diagnostic and treatment options such as component-resolved diagnostics, basophil activation testing, and oral immunotherapy are under development but are not ready for mainstream clinical application.

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