What is the appropriate management for a patient who develops an urticated (hives) rash on their back 1 day after receiving an iron infusion?

Management of Urticarial Rash After Iron Infusion

This is a delayed mild infusion reaction that should be treated symptomatically with a second-generation antihistamine (loratadine 10 mg orally or cetirizine 10 mg orally/IV), and the patient should be reassured that this is self-limiting. 1

Understanding the Clinical Picture

This presentation represents a delayed minor infusion reaction occurring 1 day post-infusion, which is distinctly different from acute anaphylaxis:

• Delayed reactions (occurring hours to days after infusion) commonly manifest as urticaria, arthralgias, myalgias, fever, and flu-like symptoms 1
• These reactions typically last up to 24 hours and are self-limiting 1
• True anaphylaxis from IV iron is exceedingly rare (<1:250,000 administrations) and would have occurred during or immediately after the infusion 2, 3

Immediate Management Steps

Symptomatic Treatment

• Administer a second-generation antihistamine: loratadine 10 mg orally OR cetirizine 10 mg IV/orally 1
• Avoid first-generation antihistamines (diphenhydramine): these can paradoxically worsen hemodynamic status by causing hypotension, tachycardia, diaphoresis, and sedation 1
• Consider NSAIDs if accompanying arthralgias or myalgias are present 1

What NOT to Do

• Do not administer vasopressors - they can convert minor reactions into serious adverse events 1
• Do not treat aggressively with corticosteroids unless symptoms persist beyond 15 minutes or worsen 1
• Do not assume this is anaphylaxis - the timing (1 day later) excludes acute hypersensitivity 1, 3

Monitoring and Follow-Up

• Reassure the patient that symptoms should resolve within 24 hours 1
• If symptoms persist beyond a few days, evaluate for other pathologies including treatment-emergent hypophosphatemia (particularly with ferric carboxymaltose) 1
• No extended observation period is required since this is a delayed reaction 1

Future Iron Infusions

Rechallenge is appropriate for future iron needs:

• This delayed urticarial reaction does NOT contraindicate future IV iron administration 1, 3
• For subsequent infusions, consider premedication with antihistamines 30-60 minutes before infusion 1
• Alternative formulations may be considered if reactions recur, though this single delayed urticarial episode does not mandate switching 1
• Start future infusions at a slower rate (50% of initial rate) and monitor for 15 minutes before increasing to full rate 1

Key Clinical Pitfalls to Avoid

Critical distinction: Delayed urticaria (1 day post-infusion) is fundamentally different from acute complement activation-related pseudo-allergy (CARPA), which occurs during or immediately after infusion 3. The 24-hour delay in this case indicates a non-IgE mediated mechanism that is benign and self-limiting 1.

Overtreatment risk: Aggressive treatment with first-generation antihistamines or vasopressors in minor reactions can actually create hemodynamically significant complications 1. The appropriate response is conservative symptomatic management with second-generation antihistamines only.