Idiopathic Anaphylaxis

Abstract

Idiopathic anaphylaxis (IA) refers to recurrent, life-threatening hypersensitivity reactions without identifiable triggers, representing a diagnostic and therapeutic challenge. We describe a 17-year-old girl presenting with recurrent episodes of flushing, pruritus, and respiratory symptoms, without consistent allergen exposure or cofactor involvement. Evaluation revealed elevated acute tryptase levels with a normal baseline, negative skin testing results, and negative galactose-α-1,3-galactose (α-gal) and KIT mutation analysis. The patient improved on daily cetirizine with no further reactions. IA remains a diagnosis of exclusion, requiring careful consideration of IgE-mediated allergies, cofactor-dependent anaphylaxis, clonal mast cell disorders, and systemic mimics such as neuroendocrine tumors or vasovagal syncope. We summarize current evidence on IA pathogenesis, epidemiology, differential diagnosis, and management. Although antihistamines and corticosteroids are commonly used prophylactically, emerging data suggest that anti-IgE therapy with omalizumab may offer benefit in refractory cases. Diagnostic workup should include serum tryptase measurement, trigger identification, and consideration of underlying mast cell disorders. Future research is needed to clarify the natural history, standardize diagnostic pathways, and evaluate long-term treatment strategies for this heterogeneous condition.

Keywords: Anaphylaxis; Idiopathic anaphylaxis; Mast cell; Mast cell activation syndrome; Tryptase.