D2.331 - An Adult Case of Cofactor-Induced Anaphylaxis Associated with Physical Exercise

Cofactor-induced anaphylaxis represents a diagnostic challenge, as standard allergy testing may be inconclusive in the absence of the triggering cofactor. Awareness of this entity is essential to prevent recurrent reactions and to guide individualized avoidance and management strategies. We report a case of cofactor-induced anaphylaxis, which shows the diagnostic complexity and clinical approach.

A 22-year-old male patient presented with generalized urticaria, angioedema of the lips and eyelids, and dyspnea occurring shortly after physical exercise. He reported similar episodes approximately five years earlier during periods of regular gym attendance, which resolved after discontinuation of exercise. No reactions occurred during the subsequent exercise-free period. Current symptoms recurred consistently following strenuous activities such as weightlifting and climbing.

Initial allergological evaluation revealed a total IgE level of 288 kU/L, with sensitization to peach, food mix, and cockroach, and borderline elevated inhalant Phadiatop IgE. Exercise under antihistamine prophylaxis was recommended; however, symptoms recurred despite premedication, leading to emergency department admission requiring systemic corticosteroids and antihistamines.

A detailed dietary history did not identify a consistent culprit food prior to exercise. The patient denied the use of nonsteroidal anti-inflammatory drugs or alcohol. Occasional consumption of bread before exercise was reported without a reproducible temporal association. Evaluation for chronic urticaria did not reveal an underlying etiology.

Skin prick testing performed at our clinic demonstrated sensitization to house dust mites, dog and cat dander, apple, and peach. Given the strong clinical suspicion of cofactor-induced anaphylaxis, component-resolved diagnostics were performed, revealing sensitization to multiple non-specific lipid transfer proteins and several tropomyosins, indicating broad cross-reactivity.

The patient received counseling regarding food allergy and cofactor-related risks. As a definitive trigger could not be identified and the risk of recurrence persisted, an epinephrine auto-injector was prescribed. Omalizumab (300 mg every 28 days) was initiated, and antihistamine therapy was optimized. An exercise challenge is planned to facilitate a safe return to physical activity.

Conclusion

This case highlights the importance of considering cofactor-induced mechanisms in patients with exercise-related anaphylaxis, particularly in the presence of polysensitization to cross-reactive allergenic proteins. Component-resolved diagnostics play a key role in risk stratification and individualized management.