D3.347 - Idiopathic Anaphylaxis: A Diagnostic Challenge

Introduction: Anaphylaxis is an acute, potentially life‑threatening systemic hypersensitive reaction that requires prompt recognition and management. While an identifiable trigger can be determined in most pediatric cases, a subset of patients experience episodes with no apparent cause, classified as idiopathic anaphylaxis.

Case report: We report the case of a sixteen‑year‑old boy, with a history of asthma and allergic rhinitis, who began experiencing episodes of anaphylaxis in 2024. The episodes were characterized by abdominal pain, flushing, auricular angioedema, and cough accompanied with dyspnoea. During regular allergology follow-ups, he experienced six episodes of anaphylaxis of unknown etiology. His baseline serum tryptase level was within the reference range, and ISAC testing did not identify any clinically relevent sensitizations.

Mast cell stabilization therapy was initiated, including antihistamines and montelukast. The patient remained symptom‑free for six months, after which the therapy was discontinued. Shortly afterwards, he developed new episodes, prompting the reintroduction of therapy, though he continued to experience further reactions. During one episode, an elevation in serum tryptase level was documented, confirming mast cell activation.

Genetic testing for systemic mastocytosis (KIT D816V) and hereditary alpha‑tryptasemia (TPSAB1) was negative. Dermatological evaluation excluded signs of cutaneous mastocytosis. REMA score was normal. Notably, all episodes appeared to occur after ingestion of histamine‑rich foods, and serum diamine oxidase (DAO) activity was found to be decreased. The basophil activation test using the patient’s serum on donor basophils to assess FcεRI activation was negative.

Based on these findings, a low‑histamine diet was introduced in combination with continued antihistamine and leukotriene receptor antagonist therapy, resulting in complete remission of symptoms.

Conclusion: This case illustrates non-IgE-mediated anaphylaxis likely driven by direct mast cell activation through histamine receptors (H1/H4), worsened by low DAO and histamine-rich foods.