Do autoimmune conditions increase the risk of side effects after iron infusions?

Autoimmune Conditions and Increased Risk of Side Effects After Iron Infusions

Patients with autoimmune conditions may experience increased side effects after iron infusions due to their altered immune response and complement activation mechanisms. 1

Mechanism of Increased Risk

Iron infusions can trigger two types of reactions in patients, with autoimmune conditions potentially increasing the risk of both:

1. Complement Activation-Related Pseudo-Allergy (CARPA)

   • Most common reaction to IV iron
   • Non-IgE-mediated hypersensitivity reaction
   • Characterized by flushing, myalgias, arthralgias, back pain, chest pressure 1
   • Patients with immune or inflammatory conditions (including systemic lupus erythematosus and rheumatoid arthritis) have an increased risk of hypersensitivity reactions 1

2. True IgE-Mediated Hypersensitivity

   • Less common but more serious
   • Can lead to anaphylaxis
   • Characterized by airway compromise, mucosal swelling, circulatory manifestations, gastrointestinal symptoms 1

Specific Concerns in Autoimmune Conditions

• Altered Iron Homeostasis: Autoimmune diseases often present with abnormal iron homeostasis, which may affect how the body processes infused iron 2
• Immune System Activation: Iron is necessary for normal immune function, and disruptions in iron homeostasis can affect immune responses 2
• Inflammation: Pre-existing inflammation in autoimmune conditions may interact with the pro-oxidant effects of IV iron 3
• Endothelial Dysfunction: IV iron can produce endothelial dysfunction, which may be exacerbated in patients with autoimmune vasculitis or other inflammatory conditions 3

Evidence in Specific Autoimmune Conditions

Rheumatoid Arthritis

• Newer, less immunogenic iron preparations (iron sucrose, low molecular weight iron dextran) have shown significant evidence of safety and efficacy in patients with rheumatoid arthritis 4
• Older concerns about disease exacerbation were primarily associated with high molecular weight iron dextran, which is now rarely used 4

Inflammatory Bowel Disease

• In a large study of 6,151 IBD patients receiving 37,168 IV iron infusions, adverse events were rare (only 1.3% of patients experienced any adverse reaction) 5
• Incident rates per 1,000 infusions for any adverse event were: ferumoxytol (2.54), ferric gluconate (1.85), iron sucrose (1.74), and iron dextran (0.96) 5

Recommendations for Patients with Autoimmune Conditions

1. Use Caution with Known Risk Factors

   • Exercise caution in patients with immune or inflammatory conditions including systemic lupus erythematosus and rheumatoid arthritis 1
   • Consider these patients at increased risk of hypersensitivity reactions 1

2. Choose Appropriate Iron Formulation

   • Consider newer, less immunogenic iron preparations for patients with autoimmune conditions 4
   • Ferric carboxymaltose and iron derisomaltose may be preferable as they require fewer infusions 6

3. Monitor Appropriately

   • Observe patients for at least 30 minutes following each IV iron injection 1
   • Be prepared to manage both CARPA reactions and true hypersensitivity reactions 1

4. Manage Reactions Appropriately

   • For mild-moderate reactions: slow or temporarily stop infusion, monitor vital signs 1
   • For severe reactions: stop infusion, implement anaphylaxis protocol 1
   • Avoid first-generation antihistamines (diphenhydramine) as they may exacerbate hypotension and other symptoms 1

Special Considerations

• Hypophosphatemia: Monitor for hypophosphatemia, especially with ferric carboxymaltose, which has higher rates (58%) compared to iron derisomaltose (4%) or iron sucrose (1%) 1

• Active Infection: Use IV iron with caution in patients with acute or chronic infection; treatment should be stopped in patients with ongoing bacteremia 1

• Monitoring After Infusion: Consider monitoring iron status 8-12 weeks after completion of therapy, with target parameters including hemoglobin ≥11-12 g/dL, ferritin >100 ng/mL, and transferrin saturation >20% 6

By understanding these risks and implementing appropriate precautions, iron infusions can be safely administered to most patients with autoimmune conditions when clinically indicated.