Current Allergy and Clinical Immunology - March 2008

Table IV. Adverse effects of IVIG therapyImmediate infusion-related* Transmission of infective agents* Consequences of increasingserum IgG †Mild to moderate reactions – Hepatitis C – several outbreaks to Renal – reversible renal impairmentheadaches, backache, chills, date; additional anti-viral step (majority of cases), acute renal failurenausea, muscle pain – occur introduced by most manufacturers in mixed cryoglobulinaemiain approximately 1% of following last outbreak in 1994infusions and are largelyHaematological – cerebal and coronaryrate-related ? Prions – potential risk; no thromboses, acute haemolysis,documented cases to dateneutropeniaSevere – anaphylaxis mayNeurological – acute aseptic meningitisoccur very rarely in IVIGDermatological – eczema, urticaria,recipients who have higherythema multiforme cutaneoustitres of anti-IgA antibodiesvasculitis*May occur with either low or high-dose IVIG; † predominantly associated with high-dose IVIG.Adapted from Jolles et al. 6 Table V. Costs of IVIG in South Africa (December 2007)more commonly associated withacute renal failure. The more importantand commonly seen IVIGinducedadverse effects are summarisedin Table IV.The risk of infectious complicationsis low. There are stringent requirementsfor donor screening andtransmissible disease testing. Themanufacturing process includessteps of viral inactivation orremoval to protect against infectiousagents that might be presentdespite screening procedures.Hepatitis B and HIV have neverbeen transmitted through IVIG and there is no knowncase of transmission of Creutzfeldt-Jakob disease.Since 1984 transmission of hepatitis C has been reported10 times and is estimated to have involved 4 000patients worldwide. 3 Further antiviral steps of pasteurisation,nanofiltration or solvent detergent treatmenthave been added to the manufacturing procedures todecrease this risk.IVIG is a product made from large pools of humanplasma and thus infectious disease transmissionalways remains a possibility. The risk of infection fromhuman plasma preparations can never be completelyruled out.The effect of live vaccines may be inhibited if IVIG isused. It is recommended that these vaccines be given3 months after the last dose of IVIG.COST OF IVIGIn 1997 there was a worldwide shortage of IVIG due todisruption of production caused by the need for USbasedplasma fractionators to comply with more stringentUS FDA requirements. Intravenous immuneglobulin costs between R220 and R350 per gram(depending on quantity bottled) (Table V). These costsdo not include the costs associated with administrationof IVIG.CONSIDERATIONS IN THE USE OF IVIGBecause of the cost, shortages and growing use ofIVIG there have been attempts in many countries todevelop guidelines for monitoring of and indications forthe use of IVIG. 1,7,10,27 Clinicians should limit their prescriptionof IVIG to conditions for which efficacy isPatient Schedule Cost of IVIG0.5 g/kg 2.0 g/kg20 kg child 1 dose R 2 853 R 9 0981x monthly/yr R 37 089 R 118 2741x 3-weekly/yr R 48 501 R 154 66670 kg adult 1 dose R 8 000 R 31 0001x monthly/yr R 104 000 R 403 0001x 3-weekly/yr R 136 000 R 527 000supported by evidence-based studies. In South Africa itmust be ensured that that the patients who will benefitmost from IVIG (determined from evidence-basedguidelines) will have access to this treatment. It isimportant to recognise that IVIG products vary in theircomposition and these differences have clinical implicationsparticularly when used for immunomodulation.28Although there is statutory documentation for the useof blood, there are no guidelines for the use or monitoringof IVIG in South Africa although it has beenrecognised that this would be valuable. It is advisedthat clinicians:• Document product, lot number and dose ofimmunoglobulin used in patients• Document the indication for the IVIG• Monitor liver function tests and viral screens, pretherapyand serially throughout IVIG therapy• Record any side-effects.Declaration of conflict of interestThe author declares no conflict of interest.REFERENCES1. Constantine MM, Thomas W, Whitman L, et al. Intravenousimmunoglobulin utilization in the Canadian Atlantic provinces: areport of the Atlantic Collaborative Intravenous Immune GlobulinUtilization Working Group. Transfusion 2007; 47: 2072-2080.2. Bruton OC. Agammaglobulinaemia. Pediatrics 1952; 9: 722-728.3. Chapel HM. Safety and availability of immunoglobulin replacementtherapy in relation to potentially transmissable agents. Clin ExpImmunol 1999; 118: S29-S34.4. World Health Organization. Appropriate uses of humanimmunoglobulin in clinical practice: Memorandum from anIUIS/WHO meeting. WHO Bulletin 1982: 60; 43-47.30 Current Allergy & Clinical Immunology, March 2008 Vol 21, No. 1