SATURDAY

November 8

SESSION 1

8:20 – 8:35

INTRAVENOUS IMMUNOGLOBULIN (IVIG) USE IN DERMATOLOGY IN CANADA

Neil Shear

History:
Immunoglobulin therapy was introduced in the 1950’s for the treatment of X-linked agammaglobulinemia. It is currently licensed in Canada for the treatment of primary and secondary immunodeficiency diseases, allogeneic bone marrow transplantation, B-cell chronic lymphocytic leukemia, pediatric HIV infection, Kawasaki disease, and idiopathic thrombocytopenic purpura. In addition, IVIG has been used in a variety of other immune-mediated indications including transplantation medicine and autoimmune and inflammatory diseases. Due to IVIGs immune-regulatory effects, several attempts have been made to use IVIG therapy in various skin diseases. The best accepted of those are toxic epidermal necrolysis and pemphigus vulgaris (and related diseases).

Different products:
IVIG is a concentrated preparation of pooled polyclonal human antibodies obtained from thousands of healthy donors. The large number of plasma donors contributing to the plasma pool provides IVIG preparations with a complete collection of antibodies directed against non-self and self-antigens. IVIG is composed largely of monomeric IgG, with small amounts of IgA and trace amounts of IgM. Several manufacturers of fractionated blood products dominate the IVIG supply market worldwide. Currently 4 licensed IVIG products are provided by Canadian Blood Services: 10% CBS/Hema-Quebec IVIG (manufactured by Bayer from Canadian plasma), GamimuneâN S/D10% (manufactured by Bayer), Gammagard S/D, and Iveegam (both manufactured by Baxter). In 2003, Bayer is supplying approximately 80% of Canada’s IVIG. The company introduced IVIG in the early 1980’s and has played a leading role in setting worldwide industry standards in the preparation of plasma for IVIG production, including donor screening, plasma procurement, plasma testing, process control, and quality assurance procedures. The newest product is Gamunexä. This is a 10% IVIG produced by caprylate virus inactivation and column chromatograpy. The Gamunex process requires significantly fewer steps, has a 70% shorter processing time, yields up to 30% more IgG, and produces a more purified final product compared with current products. Gamunex may be safely given at much faster rates, having the potential to reduce the patient’s infusion time up to 50%.

Clinical use:
IVIG has been considered a major advance in the treatment of TEN and in some centres is considered first line therapy. Mortality has been reported to decrease from 15 - 20% to 10%. But the results from all studies are not in agreement. No controlled studies have been published. IVIG is used in our Burn Unit for TEN. The dose is 1 gram / kg body weight /day for 3 days. This is based on the recent studies of a Swiss group (1), where total doses greater than 2.5 grams / kg had the best results.

In pemphigus IVIG is a useful second-line therapy. A recent review (2) suggested that doses of 1 gram / kg body weight / day for 2 days and repeated monthly to start, was a simple and useful protocol. But for pemphigus there have been no controlled studies.

Adverse reactions associated with the use of IVIG are usually mild and self-limiting (<1% of patients). Reactions such as headache, back pain, chills, flushing, fever, hypertension, myalgia, nausea and vomiting appear to be related to infusion rate rather than the dose. Patients with a history of migraine have a greater frequency of developing headaches. High infusion rates and high doses are potential risk factors for thrombotic events in at-risk patients.

References:
(1) Prins C, et al. Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases. Arch Dermatol. 2003 Jan;139(1):26-32.

(2) Ahmed AR, Dahl MV. Consensus statement on the use of intravenous immunoglobulin therapy in the treatment of autoimmune mucocutaneous blistering diseases. Arch Dermatol. 2003 Aug;139(8):1051-9.