Discussion
In this study we have shown that sensitization to alpha-gal was the predominant cause (52.3%) of IA in patients presenting to our clinic. 12 (35.3%) had consumed red meat prior to developing anaphylaxis and therefore, alpha-gal allergy is likely to be the most likely trigger in these patients. 16/34 patients who were sensitized had never consumed any red meat, as red meat consumption is not frequent among many ethnic groups in Sri Lanka. Therefore, although they did have specific IgE to alpha-gal possibly following a tick bite, it is not clear if the presence of alpha-gal specific antibodies played a role in causing anaphylaxis, in these patients. Interestingly, 14/34 patients who were found to be sensitized to alpha-gal had consumed milk products and not red meat prior to the reaction. 3 of these patients had consumed fermented buffalo milk and not cow’s milk. It has been shown that many individuals who are sensitized to alpha-gal react to different types of daily products, with 70 to 90% of individuals with alpha-gal allergy reacting to milk products in different studies [18, 19]. It was shown that although patients with alpha-gal allergy did not react to the main allergens in cow’s milk, they reacted to bovine-γ-globulin, lactoferrin and lactoperoxidase [19]. Therefore, it is possible that in the 14 patients with alpha-gal allergy who developed anaphylaxis following ingestion of milk, was due to sensitization to these components in milk.
Two patients developed anaphylaxis following consumption of gelatine containing products and were also found to have specific antibodies to alpha-gal. Alpha-gal has been reported in gelatine containing products previously [8], and therefore, the presence of alpha-gal in these products could have triggered anaphylaxis in these two patients. In fact, individuals who do not have any specific IgE to gelatine but have specific IgE to alpha-gal have shown to develop anaphylaxis following administration of vaccine, which has been shown to be due to the alpha-gal component in gelatine [20-22]. Therefore, it is recommended that gelatine containing vaccines should be administer with caution or should be avoided if possible in those with alpha-gal allergy [21].
The other causes of anaphylaxis in our cohort could be wheat dependent exercise induced anaphylaxis, and hidden ingredients or contaminants in food such as shrimp and cashew. Three of our patients had specific IgE to omega-5-gliadin and we previously reported that wheat dependent exercise induced anaphylaxis was a frequent cause in patients referred to allergy clinicals in Sri Lanka, possibly because of the difficulty in diagnosis [9, 13]. Seven of our patients also had specific IgE to tropomycin, although only 4 of them reported symptoms following ingestion of shrimps. Although the presence of specific IgE to tropomyosin is considered to be a good predictor of allergy to shrimp, tropomyosin in house dust mite, has shown to strongly cross react with shrimp tropomyosin [23, 24]. While generation of such cross reactive IgE in those who have allergy to house dust mite, are shown to sometimes cause reactions to shrimp, this is not the case in all instances [24].
A large proportion (64.7%) of patients had other allergic diseases such as allergic rhinitis (41.2%), asthma (29.4%) and atopic dermatitis (3, 8.8%), suggesting that these individuals had many IgE mediated diseases. Many (32.3%) had specific IgE to house dust mite, 24.6% to grass pollen and 13.5% to tree pollens, with some being sensitized to multiple allergens. Therefore, in addition to the allergens tested by skin prick tests and ISAC ImmunoCap, they could be sensitized to other unidentified allergens, which triggered their anaphylaxis. Although it is recommended that serum tryptase to be done in all individuals presenting with IA, due to limitations in funding, we only did this test in those, in whom a trigger could not be identified. All such individuals, had serum tryptase within the normal range, suggesting that they are unlikely to have a mast cell disorder.
In summary, a large proportion of patients presenting with IA were found to be sensitized to alpha-gal, which was the likely cause of their anaphylaxis. Importantly, 14/34 individuals developed anaphylaxis following ingestion of milk products and 2/34 after ingestion of gelatine. As these products are also shown to contain alpha-gal, it would be important to test for the presence of alpha-gal allergy in those who present with IA, due to the presence of alpha-gal in these products.