Department of Medicine

Food Allergies, Anaphylaxis and Mast Cell Disorders

Mar 6, 2019
Author: 
Dr. Peter Vadas

Dr. Peter VadasDr. Peter Vadas Allergic reactions to foods may range from mild to fatal. Individuals with a prior history of mild allergic reactions often go on to have life-threatening anaphylaxis. Risk factors for severe or life-threatening reactions to foods include (i) presence of co-existent asthma, (ii) prior history of reactions with upper or lower airway involvement (iii) allergies to peanuts, tree nuts, fish, shellfish, (iv) an underlying mast cell disorder and (v) delayed administration of epinephrine. Ten foods account for the vast majority of food-induced allergic reactions: peanut, tree nuts, cow’s milk, egg, wheat, soy, fish, shellfish, mustard and sesame seed. Currently, the standard of care requires identification or confirmation of the suspected food trigger, risk factor modification, avoidance of high risk situations and early administration of epinephrine during a reaction. On August 13, 2018, the FDA granted breakthrough therapy designation for Xolair (omalizumab) for the prevention of severe allergic reactions following accidental exposure to one or more foods in people with food allergies. In Canada, Xolair is indicated for treatment of moderate to severe allergic asthma and chronic spontaneous urticaria. Stay tuned for announcements from Health Canada for this new indication.

Some patients with food allergies require a requisite co-factor to trigger an allergic reaction. For example, patients with wheat-dependent exercise induced anaphylaxis require both ingestion of wheat and strenuous exertion to trigger an anaphylactic reaction. These co-factors may include exercise, NSAIDs, infection, ethanol consumption or menses. The food protein most commonly associated with a co-factor requirement is omega-5 gliadin in wheat. Food allergies often arise because of cross-reactivity with aeroallergens, such as tree, grass or ragweed pollens. Latex allergy can predispose to cross-reactions with avocado, kiwi, banana and chestnut. Other cross-reactive syndromes include cat – pork syndrome, alternaria – spinach syndrome and dust mite – shrimp syndrome (due to structurally homologous tropomyosin). Contamination of honey with pollens or bee venom proteins may cause anaphylaxis in sensitized individuals. Allergy to galactose-alpha-1,3 galactose (also known as alpha-gal) causes anaphylaxis to red meats, including beef, pork and lamb. Alpha-gal allergy commonly develops after a bite by the lone star tick. The tick typically first feeds on an animal and then bites a human, leading to IgE-mediated sensitization to animal erythrocyte alpha-gal. Alpha-gal allergy may predispose to severe reactions to medications, such as rattlesnake anti-venom, biologics including Cetuximab, and products containing gelatin, including some vaccines or gel-based products. Heart valves harvested from pigs have been reported to causes reactions or rapid degradation and failure of the implant in alpha-gal allergy.

Celiac disease is a common immune-mediated enteropathy triggered by gluten hypersensitivity in genetically susceptible individuals with HLA-DQ2.5. The immunodominant T cell epitopes are well-characterized and recognized by pathogenic CD4+ T cells. Nexvax2 is a peptide-based disease modifying therapeutic vaccine formulated with three specific gluten proteins, administered intra-dermally. A phase 1 trial of Nexvax2 has shown a good safety profile with efficacy studies to follow.

Eosinophilic esophagitis (EoE) is triggered by immune sensitivity to food in the majority of affected individuals. Treatment of EoE is either testing-directed or by empiric food elimination. In a study of over 1200 subjects with EoE using a high-density ImmunoChip platform encoding for 200,000 variants of autoimmune disease, there was no association with genetic variants of major histocompatibility complex (MHC) class I, II or III genes. However, an EoE risk locus at 16p13 with genome-wide significance (P combined=2.05 × 10-9, odds ratio = 0.76-0.81) was identified. This locus is known to encode for the genes CLEC16A, DEXI, and CIITI, which are expressed in immune cells and esophageal epithelial cells.

Systemic mastocytosis (SM) is a clonal disorder of mast cells that often presents with features of mast cell activation, including anaphylaxis. In a study of 122 patients with SM, risk of anaphylaxis was associated with absence of cutaneous mastocytosis, higher degree of atopy, higher total IgE levels and lower baseline tryptase levels (<40 ng/ml), as compared to patients with SM but without anaphylaxis. In those patients with mast cell disorders, treatment with mast cell stabilizers, such as ketotifen, cromolyn and omalizumab, has been shown to be highly effective.

Reactions to stinging insects (including honey bee, paper wasp, yellow jacket and hornets) can also provoke life-threatening allergic reactions, especially among people with other co-morbidities, such as asthma, cardiovascular disease and those with underlying mast cell disorders. About 7% of adult patients with Hymenoptera venom anaphylaxis have systemic mastocytosis, most commonly males without skin lesions, and anaphylaxis characterized by hypotension and loss of consciousness in the absence of urticaria and angioedema. Venom immunotherapy is about 98% effective in preventing anaphylaxis in subsequent stings. Patients with Hymenoptera venom allergy and mastocytosis have to undergo lifelong venom immunotherapy to prevent potentially fatal sting reactions.

Whereas imatinib (Gleevec) is effective in treating SM in patients with wild-type (ie unmutated) KIT, the common D816V KIT mutation is resistant to treatment with imatinib. Midostaurin and avapritinib are currently in clinical trials to treat highly symptomatic patients with indolent SM with or without common KIT mutations. Patients treated with avapritinib experienced rapid and durable disease control with an overall response rate of 72%. 56% of patients had a complete or partial response, and no patients discontinued treatment due to adverse events.