الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 122 |  |  |
| | | from | 122 | | |
Abstract
The intravenous administration of exogenous pooled human immunoglobulin (intravenous immunoglobulin- IVIg) was originally licensed as antibody replacement therapy in patients with primary immunodeficiencies. However, subsequently it has been successfully used in a host of diseases not amenable to other modalities of treatment. There are currently six FDA-approved uses for this agent. Despite a current lack of FDA approval, off-label treatment of a multitude of dermatologic disorders with IVIg has shown exciting potential for this unique treatment modality. The dermatoses successfully treated with IVIg include autoimmune bullous diseases, connective tissue diseases, vasculitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and infectious disorders (such as streptococcal toxic shock syndrome). Currently the biggest drawback in the consideration of IVIg therapy in dermatologic disorders is the lack of randomized controlled trials (RCTs). Nevertheless, there is a significant body of evidence demonstrating the efficacy of IVIg in patients with skin diseases that are resistant to treatment with standard agents.
Intravenous immunoglobulin (IVIg) is a sterile highly purified IgG preparation made from pooled human plasma and typically contains more than 95% of unmodified IgG, which has functionally intact Fe-dependent effector functions and only trace amount of IgA or IgM. It is composed of polyspecific immunoglobulin molecules prepared by cold ethanol fractionation of pooled human sera harvested from thousands of donors.
Several measures are used to ensure the safety of the product:
1. Careful selection of donors
2. Screening of every donation for hepatitis B surface antigen, antihepatitis C virus antibodies, anti-HIV 1 and 2 antibodies, syphilis serology and normal liver function
3. Use of viral inactivation procedure in addition to the already high viral inactivation afforded by cold ethanol fractionation
The mechanism by which high-dose intravenous immunoglobulin (hd IVIg) mediates anti-inflammatory activity is not well understood. These effects are mediated via the Fc portion of IgG or the antigen-binding site and the variable regions of the antibody molecule. Proposed mechanisms of action of hd IVIg include the following : 1. Anti-idiotype interactions.2. Fc receptor modulation. 3.Modulation of the production of cytokines and cytokine antagonists . 4 .Neutralization of causative microbe or toxin .5. Superantigen neutralization .6.Effects on complement - inhibition of complement-mediated damage.7. Acceleration of IgG catabolism.
Peak serum concentrations occur immediately after intravenous injection and are dose related. Within 24 hours, up to 30% of the dose may be removed by distribution and catabolism. IVIg distributes itself throughout the intravascular (60%) and extravascular (40%) spaces, crosses the placenta and may be excreted into milk. Serum half-life is 3 to 5 weeks.
High-dose IVIg is useful for patients when :
1. Conventional therapy has failed.
2. Significant adverse effects of conventional therapy exist.