Pseudoallergy

Pseudoallergy refers to clinical reactions that resemble allergic responses but occur without exposure to allergen-specific immune mechanisms, such as IgE antibodies or T-cell sensitization. These reactions can mimic true allergies in presentation and timing but are mediated by non–IgE pathways. The term anaphylactoid reaction is a historical synonym that is now used less often, with pseudoallergy preferred to distinguish non–IgE-mediated processes from IgE-mediated allergies.

Pathophysiology of pseudoallergy includes direct mast cell degranulation, alternative immune pathways such as complement activation, and receptor-mediated activation of mast cells that does not involve IgE. A notable mechanism involves the MRGPRX2 receptor on mast cells, which can be triggered by various drugs and substances, leading to rapid release of histamine and other mediators. Reactions can be dose-dependent and may occur upon first exposure to a substance, since they do not require prior sensitization.

Common triggers include radiocontrast media, certain antibiotics and opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), vancomycin (causing “red man” or infusion reactions), and some other drugs that provoke direct histamine release or complement activation. Reactions typically present with urticaria, flushing, angioedema, wheezing, hypotension, or other symptoms resembling allergic anaphylaxis, usually within minutes to hours of exposure.

Diagnosis relies on clinical history and exclusion of IgE-mediated allergy. Skin testing or specific IgE measurements are not informative for pseudoallergic reactions. Management focuses on removing or avoiding the triggering agent and treating symptoms with antihistamines, corticosteroids, or epinephrine in severe cases. In some high-risk settings, premedication or desensitization protocols may be considered under medical supervision.