Ben-Shoshan M, Cem A, Cook VE, Khalaf R, Freigeh G
The journal of allergy and clinical immunology. In practice •
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.
Saunders MN, Rival CM, Mandal M, Cramton K, Rad LM, et al.
Frontiers in allergy •
IgE antibodies against the mammalian oligosaccharide allergen galactose-α-1,3-galactose (αGal) can result in a severe allergic disease known as alpha-gal syndrome (AGS). This syndrome, acquired by tick bites that cause αGal sensitization, leads to allergic reactions after ingestion of non-primate mammalian meat and mammalian-derived products that contain αGal. Allergen-specific immunotherapies for this tickborne allergic syndrome are understudied, as are the immune mechanisms of allergic desensitization that induce clinical tolerance to αGal. Here, we reveal that prophylactic administration of αGal glycoprotein-containing nanoparticles to mice prior to tick protein-induced αGal IgE sensitization blunts the production of Th2 cytokines IL-4, IL-5, and IL-13 in an αGal-dependent manner. Furthermore, these effects correlated with suppressed production of αGal-specific IgE and hypersensitivity reactions, as measured by reduced basophil activation and histamine release and the systemic release of mast cell protease-1 (MCPT-1). Therapeutic administration of two doses of αGal-containing nanoparticles to mice sensitized to αGal had partial efficacy by reducing the Th2 cytokine production, αGal-specific IgE production, and MCPT-1 release without reducing basophil activation or histamine release. These data identify nanoparticles carrying encapsulated αGal glycoprotein as a potential strategy for augmenting αGal-specific immune tolerance and reveal diverse mechanisms by which αGal nanoparticles modify immune responses for established αGal-specific IgE-mediated allergic reactions.
The aim of this systematic review is to present the proposed theories of pathogenesis for idiopathic anaphylaxis (IA), to discuss its classification, its diagnostic approach, and management. IA represents a major diagnostic challenge and is diagnosed when excluding the possible identifiable triggers of anaphylaxis. The current research, however, revealed that certain conditions including mastocytosis, mast cell activation syndromes, and hereditary alpha tryptasemia can masquerade and overlap with its symptomatology. Also, newly identified galactose-alpha-1,3-galactose mammalian red meat allergy has recently been recognized as underlying cause of anaphylaxis in some cases that were previously considered as IA. IA comprises a heterogenous group of conditions where, in some cases, inherently dysfunctional mast cells play a role in pathogenesis. The standard trigger avoidance strategies are ineffective, and episodes are unpredictable. Therefore, prompt recognition and treatment as well as prophylaxis are critical. The patients should always carry an epinephrine autoinjector.