Özge Öztürk AKTAŞ, Ebru DAMADOĞLU, Gül KARAKAYA, Ali Fuat KALYONCU
Acta Medica - 2026;57(3):266-272
Objective: Although hypersensitivity reactions to oral iron preparations are rare, they are clinically challenging as they can limit treatment options for iron deficiency anemia. Data on cross-reactivity between different oral iron formulations are limited, and guidance on safe switching strategies is insufficient. This study aimed to define the clinical characteristics of patients with suspected oral iron hypersensitivity and to evaluate the tolerance of alternative oral iron preparations using supervised oral provocation testing. Materials and Methods: We retrospectively analyzed 18 adult patients who presented to a tertiary allergy clinic with a history of hypersensitivity to an oral iron preparation between June 2011 and June 2025. Alternative oral iron formulations were selected based on differences in iron valence ferrous (Fe²?) and ferric (Fe³?) and ligand or complex structure. Oral provocation tests were performed using graded protocols. Results: The cohort included 17 females and 1 male with a mean age of 42.7 +/- 9.5 years. Most reactions were attributed to ferrous (Fe²?) salts (77.8%), whereas ferric (Fe³?) salts accounted for 22.2% of the culprit oral iron formulations. The most frequent symptom was skin symptoms (77.8%), followed by angioedema or mucosal involvement (38.9%), systemic or vasovagal-like symptoms (27.8%), and gastrointestinal complaints (11.1%). Three patients experienced clinically anaphylactic reactions. Alternative iron formulations were selected by altering the iron oxidation status and/or ligand structure. All oral provocation tests with alternative preparations, including extended provocation protocols, were negative (100%), indicating excellent tolerance and a low probability of clinically significant cross-reaction. Conclusion: In patients suspected of having oral iron hypersensitivity, switching to an alternative oral iron preparation with a different oxidation state and/or ligand by performing provocation tests appears to be a safe and effective strategy. These findings support that hypersensitivity reactions are more closely related to formulation-specific components than to iron itself, and offer a practical approach to maintaining oral iron therapy.
