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Intravenous Iron Reactions: Insights from an Allergy and Immunology Perspective
Journal article   Open access

Intravenous Iron Reactions: Insights from an Allergy and Immunology Perspective

Jordon Jaggers, Cosby Stone Jr., Matthew Krantz and Elizabeth Phillips
The journal of allergy and clinical immunology. Global, Vol.4(4), 100543
2025
DOI: https://doi.org/10.1016/j.jacig.2025.100543
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CC BY V4.0,  Open Access

Abstract

Background Diagnosis and management of intravenous iron reactions is often challenging as skin testing has unproven utility and most reactions are non-IgE-mediated. Objective We aimed to identify clinical patterns and tolerability predictors in patients with intravenous iron reactions. Methods We conducted a retrospective cohort study of intravenous iron reactions referred to Vanderbilt University Medical Center Drug Allergy Clinic from 04/2014-01/2025 and administered a follow-up survey via RedCap to evaluate patient outcomes with future intravenous iron administration. Results Among 51 patients presenting for intravenous iron adverse reactions, skin testing was deemed negative in all 48 (100%) tested. Notable labs within one year of reaction were low vitamin D (47%), high parathyroid hormone (46%), and low phosphorus (10%). Many patients (56%) were dermatographic and drug alert labels included opioids (31%), fluoroquinolones (14%), and radiocontrast dye (8%). Following assessment, 31 patients received intravenous iron (61%), using same (n=15, 48%) and/or different (n=17, 55%) formulations than initially implicated with various modifications including antihistamines, slower infusion rate, and intravenous fluid pretreatment. Of these 31 patients, 27 (87%) tolerated the infusions. Additionally, following evaluation, patients were surveyed regarding future intravenous iron administrations, with 29% response rate (n=15). Of responders, seven patients (47%) reported receiving intravenous iron after evaluation and all reported tolerance. Conclusion Most intravenous iron reactions are non-IgE-mediated; however, our study introduces two novel observations including a high frequency of dermatographism (56%) and common co-labeling of these patients with drug alerts to MRGPRX2-activating drugs suggesting a possible shared pathophysiologic mechanism.

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