Persistence, Severity, and Reactivity Thresholds in Fish-Allergic Patients Sensitized to Parvalbumin

Background: Fish allergy affects children and adults worldwide, and there are transient and persistent phenotypes. Objective: We aimed to analyze persistence, severity, and reactivity thresholds in challenge-confirmed fish-allergic patients sensitized to parvalbumin. Methods: Patients 12 to 65 years old reporting immediate reactions to fish, with fish skin prick test ≥5 mm and IgE to cod and carp β-parvalbumins ≥0.70 kU_A/L, were recruited in 6 European centers. Except for the case with recent severe anaphylaxis, patients were eligible for a double-blind placebo-controlled food challenge with cod, followed, if negative, by an open food challenge. Severity of reported and elicited reactions was graded with the Food Allergy Severity Score, eliciting dose (ED) was calculated using interval-censoring survival analysis and probabilistic models, and factors associated with a positive challenge and severe reactions were analyzed by logistic regression. Results: Of 42 patients fulfilling inclusion criteria, fish allergy was confirmed in 30 (71.4%) patients. The median fish allergy duration was 23 years. Although 70% of cases reported anaphylaxis with respiratory or cardiovascular involvement, food challenges resulted in oropharyngeal symptoms (34.7%) or mild systemic reactions (73.9%), with only 1 anaphylaxis with bronchospasm (4.3%). Male sex was associated with severe reactions (odds ratio: 5.44, 95% confidence interval: 1.04-28.53). ED₁₀ for objective symptoms was 0.99 to 2.54 mg of protein. No correlation was found between severity and ED. Conclusions: Adolescents and adults with persistent fish allergy linked to parvalbumin sensitization have experienced severe allergic reactions in real life and have a low threshold of reactivity. Our findings support the need for large-scale studies and new therapeutic options for these fish-allergic patients.