Intravenous immunoglobulins in neurological disorders: safety issues.

IVIg products may be applied for the provision of antibodies in patients with primary or secondary antibody deficiency syndromes or with the aim of immune modulation in patients with autoimmune diseases. The average dose for the provision of antibodies is 400 mg/kg per month while much higher doses are needed 1 to 2 g/kg in a single or in repeated occasions in the treatment of autoimmune diseases e. g. neurological diseases. Indications for treatment have been specified at two consensus meetings (1990 and 1999) and by different groups of experts but off-label use highly exceeds the recommended indications. For this reason risk benefit assessment is of great importance. Adverse events can be categorized as (1) early inflammatory, (2) infectious, (3) rare complications of (mainly) high dose treatment. Early inflammatory reactions are known since the initiation of immunoglobulin treatment, the rate varies greatly 10%-85% and reactions can usually be dealt with by lowering the infusion rate. Viral infections e. g. transmission of viral hepatitis by IVIg have been a problem in certain products until the mid-1990s and industry responded in a fast and efficient manner. Viral safety has been achieved and all IVIg products licensed are considered to be safe in this respect. Rare complications mainly of high dose treatment: renal complications were described already in the mid-1980s they were mainly but not only linked to products containing sucrose, maltose and glucose with or without glycine. These complications are rare (88 patients reported in 30 years) and older patients and patients with conditions predisposing to renal disease were at increased risk. Thromboembolic events were another rare but severe complication of high dose treatment also associated with rapid infusion, deep venous thrombosis, pulmonary embolism, myocardial infarction and stroke have been reported. Possible mechanisms have been discussed.