CHILDHOOD ANAPHYLAXIS: NEW DEVELOPMENTS IN DIAGNOSIS AND TREATMENT

CHILDHOOD_ANAPHYLAXIS_NEW_DEVELOPMENTS _IN_DIAGNOSIS_AND_TREATMENT_kapak

ASSOCIATED COFACTORS AND COMORBID CONDITIONS

Selma Alim Aydın

Sivas Numune Hospital, Department of Pediatric Immunology and Allergic Diseases, Sivas, Türkiye

Alim Aydın S. Associated Cofactors and Comorbid Conditions. In: Harmancı K, editor. Childhood Anaphylaxis: New Developments in Diagnosis and Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.285-296.

ABSTRACT

Cofactors: A variety of cofactors have been identified that contribute to the development and exacerbation of anaphylaxis by increasing clinical severity and lowering the threshold for allergic reactions. These cofactors are thought to sensitize individuals to smaller quantities of allergens and thus play a critical role in the pathophysiology. The relevant cofactor may differ across individuals. Among the identified cofactors are physical exertion, infections, nonsteroidal anti-inflammatory drugs (NSAID) use, alcohol consumption, fever, cold exposure, emotional stress, travel and the premenstrual period. Exercise is hypothesized to enhance anaphylactic responses by increasing the bioavailability of specific allergens and lowering the activation threshold of mast cells and basophils. Infections may promote mast cell activation by modulating immune function. NSAIDs and alcohol have been shown to increase gastrointestinal permeability, facilitating the absorption of larger, more allergenic molecules. Moreover, suppression of gastric acid secretion by H2 receptor antagonists and proton pump inhibitors (PPIs) may interfere with the inactivation of ingested allergens, thereby enhancing their allergenic potential. Comorbid Conditions: Comorbid diseases and concurrent pharmacological therapies have been shown to significantly influence the clinical manifestations, severity and treatment response in anaphylactic episodes. Asthma, cardiovascular disorders, mastocytosis and along with the intake of certain pharmacological agents are recognized as key variables influencing clinical outcomes. Among these, asthma has been most frequently associated with a heightened risk of severe manifestations. Poorly controlled or severe forms of asthma are particularly linked to life-threatening reactions. Additional atopic conditions, particularly atopic dermatitis, pollen sensitization and pollen-food syndrome have been implicated in both the severity and recurrence of food-induced anaphylaxis. Atopic diseases have been associated with an increased risk of reactions triggered by non-food stimuli, such as physical exertion and latex exposure. Cardiovascular disease is considered a risk factor for fatal anaphylaxis, particularly among middle-aged and older individuals. Genetic factors such as polymorphisms in the angiotensin-converting enzyme (ACE) gene, individual variability in bradykinin metabolism and elevated baseline levels of serum tryptase and plasma histamine are considered important determinants of anaphylaxis severity in pediatric populations. In mast cell disorders, both the incidence of hypersensitivity reactions and the likelihood of severe or fatal outcomes are markedly elevated. The concomitant use of beta-blockers and ACE inhibitors has been shown to compromise compensatory responses following anaphylaxis and reduce the clinical effectiveness of epinephrine therapy. Certain medications used in the treatment of attention deficit hyperactivity disorder (ADHD) and depression may induce effects during anaphylactic reactions that resemble the side effects of epinephrine.

Keywords: Anaphylaxis; Child; Cofactors; Comorbid conditions

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