Intravenous Immunoglobulin

Intravenous immunoglobulin (IVIG) is pooled human IgG from thousands of donors. It replaces antibody in primary and secondary immunodeficiency and modulates the immune system in autoimmune and inflammatory disease. Uses include immune thrombocytopenia, Kawasaki disease, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and toxic shock syndrome.

Mechanism. At replacement doses it supplies protective antibody. At high doses (1 to 2 g/kg) it blocks Fc receptors, neutralises autoantibodies, dampens complement, and alters T and B cell and cytokine function.

Pharmacokinetics. IgG half-life is about 3 to 4 weeks. Levels peak at the end of infusion and fall to a trough before the next dose. Subcutaneous immunoglobulin (SCIG) gives steadier levels.

Choosing the product. Use a sucrose-free, low osmolality, IgA-depleted product in kidney disease, diabetes, IgA deficiency or high thrombosis risk. Products differ in concentration, osmolality and sugar content, so brand switching needs care.

Infusion rate. Start at 0.5 to 1 mL/kg/h for 30 minutes, then increase every 15 to 30 minutes to the product maximum (often 4 to 8 mL/kg/h). Slow the rate in the first infusion, in patients with thrombosis risk, and in repeat reactions.

• First-line. Primary immunodeficiency with antibody failure; Kawasaki disease; severe immune thrombocytopenia with bleeding; Guillain-Barre syndrome; chronic inflammatory demyelinating polyneuropathy.
• Alternative. Secondary immunodeficiency (chronic lymphocytic leukaemia, myeloma, after B cell depletion) with recurrent severe infection; dermatomyositis; myasthenia gravis exacerbation; autoimmune encephalitis.
• Specialist. Severe toxic shock syndrome, neonatal alloimmune thrombocytopenia, ABO-incompatible transplant desensitisation, post-exposure prophylaxis for measles and hepatitis A in selected people.
• Emergency. Bleeding in immune thrombocytopenia, Kawasaki disease, Guillain-Barre syndrome or myasthenic crisis.

Selection. Reserve for indications with good evidence, since supply is limited and cost is high. Check IgA status, renal function, hydration and thrombosis risk first.

Contraindications. Prior anaphylaxis to immunoglobulin; IgA deficiency with anti-IgA antibodies (use IgA-depleted product); hyperprolinaemia (products stabilised with proline); sucrose products in kidney impairment.

Serious adverse effects.

• Infusion reactions: headache, flushing, fever, chills, myalgia, nausea; anaphylaxis (rare).
• Thromboembolic events: stroke, myocardial infarction, venous thrombosis (risk rises with age, immobility and high doses).
• Acute kidney injury, mainly with sucrose-stabilised products and in older or diabetic patients.
• Aseptic meningitis, haemolytic anaemia (non-O blood groups), transfusion-related lung injury, neutropenia, hyponatraemia (pseudo), eczema and hyperviscosity.

Major interactions. Live vaccines (measles, mumps, rubella, varicella): delay for 3 to 11 months after high dose; nephrotoxic drugs add renal risk; false-positive serology from passive antibody transfer.

Common prescribing errors.

• Starting at a fast rate.
• Not checking renal function, hydration and sucrose content.
• Dosing by actual weight in obesity (use adjusted weight).
• Giving to patients with IgA deficiency without product choice.
• Vaccinating with live vaccines soon after.

Special groups.

• Pregnancy: used when needed; no known harm.
• Breastfeeding: acceptable.
• Children: 0.4 g/kg daily for 5 days in Guillain-Barre syndrome, 2 g/kg in Kawasaki disease, and 1 g/kg in immune thrombocytopenia.
• Older adults: lower rates, slower infusions, hydration, thrombosis review.
• Kidney: use sucrose-free product and slow rate; avoid dehydration.
• Liver: no adjustment.
• East Africa: IVIG is scarce and very costly, so reserve for Kawasaki disease, Guillain-Barre syndrome with severe weakness, and life-threatening immune thrombocytopenia; exclude HIV-related thrombocytopenia first, since antiretroviral therapy treats it.

Monitoring. Pulse, blood pressure, temperature and respiratory rate at baseline, 15 minutes, with each rate change and at the end; creatinine before and after; trough IgG in replacement; full blood count for haemolysis 7 to 10 days after; symptoms of thrombosis.

Referral and escalation. Anaphylaxis; chest pain, stroke symptoms or limb swelling; falling urine output or creatinine rise; severe headache with neck stiffness; dark urine.

Comparison with alternative classes. IVIG acts within days and avoids broad immunosuppression, but supply is limited, effects are temporary and thrombosis and renal risks apply. Glucocorticoids, plasma exchange, rituximab and thrombopoietin receptor agonists are alternatives by disease.