D2.317 - “Cutaneous Anaphylaxis to Raw Egg White in a Patient with Established Oral Tolerance: Clinical Evidence Supporting the Dual-Allergen-Exposure Hypothesis”

Introduction

Egg allergy commonly resolves through the progressive acquisition of clinical tolerance, initially to extensively heated forms and subsequently to raw egg. Its natural history is influenced by the molecular sensitization profile and the route of allergen exposure, as immune responses differ according to the target organ. Cutaneous exposure—particularly in the context of epidermal barrier disruption—may permit systemic absorption of allergenic proteins and trigger severe immediate reactions, even in individuals with established oral tolerance. This phenomenon is consistent with the dual-allergen-exposure hypothesis, which proposes that epicutaneous exposure promotes Th2-driven IgE sensitization, whereas gastrointestinal exposure favors regulatory immune responses and tolerance.

Case description

We report the case of a 14-year-old male with well-controlled house dust mite–induced asthma. During preschool years, egg sensitization was identified during evaluation for atopic dermatitis (total IgE 55 kU/L; specific IgE: ovalbumin 1.34 kUA/L, ovomucoid 0.08 kUA/L; skin prick tests: egg white 3+, yolk 2+). Egg exclusion resulted in clinical improvement. At age 6, an oral food challenge (OFC) with cooked egg was tolerated. At age 8, OFC with raw egg elicited immediate rhinitis and urticaria at a cumulative dose of 24 g. A repeat OFC at age 10 was negative, and since then, egg in all forms has been regularly consumed without adverse reactions.

At age 14, after a superficial forearm burn, raw egg white was applied topically. Within minutes, he developed generalized erythema, pruritus, urticaria, tremor, tachycardia, and hypotension (<5th percentile), fulfilling criteria for anaphylaxis and requiring intramuscular epinephrine. Symptoms resolved completely.

Post-event evaluation showed total IgE 257 kU/L; specific IgE to ovalbumin 0.25 kUA/L, ovomucoid 0.09 kUA/L, and lysozyme 0.93 kUA/L; and elevated specific IgG4 to ovalbumin (19.90 mgA/L) and ovomucoid (5.42 mgA/L). Skin testing revealed weak positivity to egg white (1+). The patient continues to tolerate egg ingestion.

Conclusions

This case demonstrates that oral tolerance does not necessarily protect against systemic reactions following epicutaneous exposure in the presence of barrier disruption. Persistent IgE to ovalbumin and lysozyme, despite elevated allergen-specific IgG4, may allow cutaneous allergen penetration and effector-cell activation. These findings provide clinical support for the dual-allergen-exposure hypothesis and underscore the importance of patient education regarding topical food application on compromised skin.