Severity of Reactions in Double-Blind Placebo-Controlled Food Challenges: New Insights From the EuroPrevall Outpatient Clinic Study.

BACKGROUND AND

OBJECTIVES

Oral food challenge, particularly double-blind placebo-controlled food challenge (DBPCFC), is the gold standard for diagnosis of food allergy, although safety concerns limit its widespread use.

Objectives

To evaluate the severity of reactions during DBPCFCs and to identify predictors of severe reactions.

METHODS

DBPCFCs from the EuroPrevall outpatient clinic study were analyzed in patients reporting immediate reactions to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple, and/or peach. Patients with prior life-threatening anaphylaxis were excluded. Reaction severity (patient-reported and DBPCFC-elicited) was assessed using the Food Allergy Severity Score. A 2-step modeling strategy based on generalized estimating equations was applied to identify predictors of a positive DBPCFC, and, among positive challenges, predictors of anaphylaxis.

RESULTS

Among 514 DBPCFCs performed, 190 (36.9%) were negative, 30 (5.8%) uncertain, and 294 (57.2%) positive (102 mild oropharyngeal reactions [19.8%] and 192 systemic reactions [37.4%], of which 160 were moderate and 32 severe). The 32 severe reactions comprised 30 cases (30/514 [5.8%]) with lower respiratory involvement (16/30 with cough or dyspnea) and 2 anaphylaxis with hypotension (2/514 [0.4%]). DBPCFC reactions were less severe than patient-reported reactions (P<.01). Atopic dermatitis and food-specific IgE >0.35 kUA/L predicted positivity, whereas prior reaction severity and egg challenge were predictors of anaphylaxis.

CONCLUSION

While systemic reactions during DBPCFCs were frequent, severe anaphylaxis was rare, supporting the safety profile of DBPCFCs when appropriately conducted. Key predictors of reactivity include atopic dermatitis and food-specific sensitization, while prior severity points to a risk of anaphylaxis. These findings may help risk stratification and patient selection in clinical practice.