Mollusk allergy in shrimp-allergic patients: Still a complex diagnosis. An Italian real-life cross-sectional multicenter study

Abstract

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly.

Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods.

Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro.

Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south.

Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity should still rely on skin tests with fresh material. The exclusion of mollusks from shrimp allergic patients' diets should occur when clinical history, available diagnostic instruments, and/or tolerance tests support such a decision.

Keywords: Anaphylaxis; Crustaceans; Food allergy; IgE diagnosis; Mollusks; Multiplex analysis; Tropomyosin; Urticaria/angioedema.

Fig. 1

The figure shows the prevalence of reactivity to the tests performed in the Italian Multicenter real-life Study on mollusk allergy in shrimp allergic patients, May 15 to November 15, 2021. (skin prick test with commercial extracts, prick - prick with fresh foods, both cooked or raw, and in vitro dosage of specific IgE to extract with ImmunoCAP singleplex method) respectively, in mollusk tolerant subjects, or with a history of an adverse reaction to cephalopods or bivalves. Significant differences are indicated in the figures (p < 0.01)

Fig. 2

Molecular sensitization profile in 98 patients allergic to crustaceans that were tolerant 40 patients) or reactors (58 patients) to cephalopods and/or bivalves. The area-proportional Venn diagrams show the logical relationship between the single molecules currently available for shrimp allergy diagnosis in the fraction of tolerant patients and the fraction who react to mollusks. The squid picture is given as an example of cephalopods and the mussel as an example of bivalves. Null refers to the percentage of patients not reactive to any molecule tested; AK: Arginine kinase; SCB: Sarcoplasmic calcium-binding protein; MLC: Myosin light chain

Fig. 3

The figure shows the comparison of the results of the tests performed in the population of the Italian Multicenter real-life Study on mollusk allergy in shrimp allergic patients. in the north compared with central-southern Italy. The results of SPTs with commercial extracts are shown in A, the differences in the IgE assay with the singleplex method (ImmunoCAP) in B, the in vivo tests with fresh, cooked or raw food in C, and the different tolerance profiles in D. to the respective foods indicated in the figure, between north and central-southern Italy. The significant differences are shown directly within the figure