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.