CHILDHOOD ANAPHYLAXIS: NEW DEVELOPMENTS IN DIAGNOSIS AND TREATMENT

CHILDHOOD_ANAPHYLAXIS_NEW_DEVELOPMENTS _IN_DIAGNOSIS_AND_TREATMENT_kapak

ENDOTYPES AND PHENOTYPES IN ANAPHYLAXIS

Fatma Bal Çetinkaya

Kocaeli City Hospital, Department of Pediatric Immunology and Allergic Diseases, Kocaeli, Türkiye

Bal Çetinkaya F. Endotypes and Phenotypes in Anaphylaxis. In: Harmancı K, editor. Childhood Anaphylaxis: New Developments in Diagnosis and Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.49-61.

ABSTRACT

Anaphylaxis is a severe and swiftly progressing systemic allergic reaction that can be life-threatening. Its clinical presentation and underlying biological mechanisms are remarkably diverse, making it a highly complex condition to understand and manage. Traditionally, anaphylaxis has been associated with IgE-mediated pathways; however, this perspective alone falls short of encompassing the broader spectrum of immunologic and non-immunologic mechanisms involved. Recent advances in immunology have introduced the complementary concepts of endotypes which define distinct biological and immunological underpinnings and phenotypes which describe observable clinical manifestations. Together, these concepts offer a more detailed and accurate framework for interpreting the pathophysiology of anaphylaxis. This chapter provides a detailed examination of the different endotypes of anaphylaxis, including those mediated by IgE, IgG, complement activation, and non-immunologic triggers. Particular focus is placed on mast cell–related disorders, such as systemic mastocytosis and mast cell activation syndromes, which are known to significantly increase the risk and severity of anaphylactic episodes. Hereditary alpha tryptasemia which is a genetic predisposition contributing to elevated baseline tryptase levels and is in association with mast cell activation syndromes is also a risk for increasing hypersensitivity. From a clinical standpoint, anaphylaxis may present in various forms: IgE-driven type I-like responses, cytokine-mediated syndromes, complement-associated reactions, or mixed profiles. These differ not only in their symptomatology and severity but also in the systems they affect and how quickly they develop. Environmental and physiological cofactors such as NSAID use, physical activity, alcohol consumption, infections, and hormonal changes can further influence the threshold and intensity of reactions. Diagnostic precision is enhanced by the use of biomarkers like serum tryptase, specific IgE, and complement fragments (C3a/C5a), alongside novel tools such as basophil activation tests and KIT gene analysis. Furthermore, biphasic and delayed-onset reactions underscore the importance of extended patient monitoring even after initial symptom resolution. Finally, the timing and progression of symptoms can vary widely based on the nature, dose, and route of allergen exposure, as well as individual patient characteristics. Ultimately, approaching anaphylaxis through the dual lens of phenotype and endotype allows for more personalized care. This integrative model not only improves diagnostic accuracy but also supports targeted therapies and better long-term outcomes in patients at risk of severe hypersensitivity reactions.

Keywords: Anaphylaxis; Endotype; Phenotype; Hereditary alpha tryptasemia; Mast cell activation syndrome

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