5 | Discussion
In our multicenter study, involving 19 centers scattered throughout
Italy, we evaluated the prevalence and the sensitization profile of
allergic subjects to crustaceans reactive or not reactive also to
mollusks
We confirmed once more (11), that the diagnostics with both the extracts
and the molecules currently available in the market is inadequate to
detect satisfactorily patients hypersensitive to crustaceans and
mollusks. We observed an extreme heterogeneity of results from one
patient to another using the common diagnostic approaches, including
skin prick testing with commercial extracts, skin testing with fresh
material and specific IgE measurements. We previously showed the
unreliability of commercial extracts for SPT available on the market due
to differences in allergenic proteins concentrations (10), thus
potentially leading to confounding results.
The currently available molecular diagnostics for seafood shows two
major pitfalls. First, not all allergen molecules are present on the
diagnostic platforms and, second, practically all the molecules
available derive from crustaceans and none from mollusks. The diagnosis
of mollusks allergy is therefore always indirect, based on the
presumption of cross-reactivity with crustaceans. Of the 58 shellfish
molecules currently registered as allergens by the WHO/IUIS Allergen
Nomenclature Sub-Committee, only 8 belong to the mollusks (see Table in
the repository). If one considers, for instance, that the tropomyosins
from mollusks share no more than 60% amino acid sequence identity with
the other allergenic tropomyosins isolated so far from crustaceans,
insects, mites, and fish (1), one can easily figure out that this might
lead to a failure in the detection of allergic patients (12). A 2018
study showed that in the pacific oyster extract, along with many
specific allergens of invertebrates, fish, and mites, can be isolated
allergens from other different biological sources such as pollen and
fungi, thus prompting interesting scenarios about possible unexpected
sources of sensitization(13).
Another interesting point of our study concerns the differences in
sensitization profiles observed in the different geographic areas of the
country. We detected that in the north sensitization to crustaceans was
much more frequent than in the center/south, where in turn sensitization
to cephalopods and bivalves was more prevalent. These differences might
be the result of different culinary habits between the North (where the
way of life is more similar to that in Central and Northern Europe) and
the South, where habits are similar to those in other Mediterranean
countries such as Greece or Spain(8). These geographical differences
could also underlie different sensitization mechanisms according to
different environmental exposures (11). This point needs to be addressed
in future studies.
The finding of three single patients who were mono-reactors to bivalves
(both oyster and mussel), suggests that primary sensitization to
mollusks is possible, albeit being an extremely rare event, sometimes
associated with sensitization also to house dust mites (14). A study
designed to verify whether reactivity is always secondary to
sensitization to mite allergens should be carried out, focusing
attention on a pediatric-only population.
Objective limitations of the study are the absence of oral food
challenge in patient selection, which was made only on the anamnestic
data, and the use of heterogeneous commercial preparations, both forin vivo and in vitro diagnostics, where it is not always
declared. by the producers, the type of crustacean, prawn or shrimp used
to prepare the extract.
In conclusion, this study clearly shows the following:
(i) current diagnostic methods are
inadequate to predict cross-reactivity between crustaceans and mollusks
due to the lack of specific mollusks allergens and because these are
only partially cross-reactive to crustacean homologue proteins; (ii) the
detection of mollusks hypersensitivity must still rely on skin tests
with fresh material (and oral challenges where possible); (iii)
clinically, there is no need to exclude a priori mollusks from shrimp
allergic patients’ diet, unless the available diagnostic instruments
support such decision; (iv) albeit rarely, primary sensitization to
mollusks seems possible although the incomplete spectrum of shrimp
allergens does not allow us to exclude that shrimp acts as primary
sensitizer also in those few cases.