Intravenous iron reactions: Insights from an allergy and immunology perspective

Diagnosis and management of intravenous iron reactions is often challenging, as skin testing has unproven utility and most reactions are non-IgE-mediated.

We aimed to identify clinical patterns and tolerability predictors in patients with reactions to intravenous iron.

We conducted a retrospective cohort study of patients with reactions to intravenous iron who were referred to the Vanderbilt University Medical Center Drug Allergy Clinic from April 2014 through January 2025 and administered a follow-up survey via RedCap to evaluate patient outcomes with future intravenous iron administration.

Of the 51 patients presenting for adverse reactions to intravenous iron, 48 had skin testing performed. The skin testing results were deemed negative in all 48 cases (100%). Notable laboratory test results within 1 year of reaction were low vitamin D level (47%), high parathyroid hormone level (46%), and low phosphorus level (10%). Many patients (56%) were dermatographic, and their drug alert labels included opioids (31%), fluoroquinolones (14%), and radiocontrast dye (8%). Following assessment, 31 patients received intravenous iron (61%) using formulations that were the same as (n = 15 [48%]) and/or different from (n = 17 [55%]) the forumlation initially implicated, with the various modifications including antihistamines, slower infusion rate, and intravenous fluid pretreatment. Of these 31 patients, 27 (87%) tolerated the infusions. Additionally, following evaluation, the patients were surveyed regarding subsequent intravenous iron administrations, eliciting a 29% response rate (n = 15). Of the responders, 7 patients (47%) reported receiving intravenous iron after evaluation; all 7 reported tolerance.

Most reactions to intravenous iron are non-IgE-mediated; however, our study introduces 2 novel observations, namely, a high frequency of dermatographism (56%) and common colabeling of these patients with drug alerts to Mas-related G protein-coupled receptor X2 (MRGPRX2)-activating drugs, suggesting a possible shared pathophysiologic mechanism.