Adverse reactions to modern IV iron are rare and usually mild. They can be grouped into three mechanistic categories:
1. Complement activation–related pseudoallergy (CARPA)
- The vast majority of reactions belong here.
- Mechanism: innate immune activation from nanoparticle–complement interaction, releasing anaphylatoxins (C3a, C5a).
- Clinical spectrum:
- Mild (“Fishbane reaction”) — transient flushing, warmth, back or chest pressure, anxiety; resolves quickly when infusion paused.
- Severe (non-Fishbane CARPA) — rarer; may include hypotension, dyspnea, or syncope; still non-IgE-mediated.
- Management: stop infusion, wait for resolution, restart at half rate; do not treat routinely with antihistamines or steroids.
2. True anaphylaxis (IgE- or IgG-mediated)
- Exceptionally uncommon (< 1 per 200,000 infusions).
- Historically associated with high-molecular-weight iron dextran (no longer marketed).
- Requires epinephrine; future exposure to same product contraindicated.
3. Other rare or delayed events
- Local infusion-site reactions (extravasation, discomfort).
- Delayed arthralgia/myalgia hours later (non-allergic, self-limited).
- Hypophosphatemia with certain formulations (esp. ferric carboxymaltose).
Summary:
Most infusion reactions to IV iron are CARPA-type events, with Fishbane reactions representing their mild, transient expression and non-Fishbane reactions their more severe form. True IgE-mediated anaphylaxis is vanishingly rare with today’s non-dextran formulations.