To the Editor The study by Dr Wang and colleagues1 reported the risk of anaphylaxis with different intravenous iron products. I have several concerns.
One concern is the definition of anaphylaxis. In the article’s online Supplement, both anaphylaxis criteria B and C include “injection of diphenhydramine.” Given that diphenhydramine often is given both as a premedication (without evidence to support its use) and for treatment of minor reactions (flushing, myalgias of the chest and back, or headache), including it in the definition has the potential to greatly overestimate anaphylaxis rates. Diphenhydramine itself has been reported to cause somnolence, tachycardia, and hypotension.2 Published data suggest that when diphenhydramine is used as premedication prior to intravenous iron, a significant majority of the reactions ostensibly attributed to the iron were due to diphenhydramine.3 In the Methods section, the authors noted that minor self-limited reactions such as minor allergic reactions would be wrongly labeled as anaphylaxis events. It would be informative to know the rates of anaphylactic reactions when patients who received diphenhydramine were excluded.
DeLoughery TG. Risk of Anaphylaxis With Intravenous Iron Products. JAMA. 2016;315(20):2232. doi:10.1001/jama.2016.0962