2 | INTRODUCTION
Seafood is included among the “Big Eight” food groups responsible for most cases of food allergy. It is estimated that depending on the different geographic areas, about 3% of the general population is allergic to shellfish (1,2). This generic term includes more than 300 different invertebrate species which are divided into two large groups: crustaceans (shrimps, crabs, lobsters etc.) and mollusks (Bivalvia , such as clam, mussels, scallops or oysters, andCephalopoda , like squids, cuttlefish or octopuses etc.)(3)(4). These taxonomic classifications are essential to predict the structural, immunological and allergological similarities that underlie a possible cross-reactivity. The availability and consumption of seafood vary greatly in different parts of the world, representing the second cause of primary food allergy in Italy, after Lipid transfer proteins (5). Even eating habits, including the different methods of food processing, may exert a strong impact on the incidence and severity of allergy to crustaceans and seafood, since in some cases physical treatments can increase or reduce IgE reactivity(6), depending on the molecule involved in patient sensitization (7). So far, it has been argued that due to the cross-reactivity among allergens in invertebrates, primarily tropomyosin, the patient allergic to crustaceans should also exclude cephalopods and Bivalvia from the diet. However, recent studies seem to suggest that this is not the case; in fact, a significant proportion of crustacean allergic patients report that they usually tolerate other invertebrates (8). One of the main diagnostic problems is that all the molecules commercially available for in vitro tests come from crustaceans and not from mollusks. As a consequence, IgE diagnostic approach for mollusks adverse reaction is always indirectly based on a presumptive but not fully demonstrated cross-reactivity, unless tests with fresh, raw or cooked cephalopod or Bivalvia are carried out, with all the drawbacks associated with such approach.
The main aims of this study were (i) to investigate the prevalence of patients allergic to crustaceans with or without cross-reactivity to cephalopods and/or bivalve mollusks; (ii) to define the molecular profile in both cross-reacting and non-cross-reacting individuals; (iii) to highlight any differences in the severity of the allergic reactions, and (iv) to investigate the geographical differences in seafood sensitization profiles in Italy.