IVIG

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Uses of IVIG

IVIG is used clinically to provide antibodies for patients with primary immunodeficiency disorders3 (the most common variants of which are X-linked agammaglobulinaemia, common variable immunodeficiency and selective IgA deficiency)4 and secondary immunodeficiencies, where it is used to reduce recurrent infections in conditions such as chronic lymphatic leukaemia, multiple myeloma, and congenital acquired immune deficiency syndrome.1-5

IVIG is also used to modulate the immune system; for example, in patients with autoimmune diseases such as idiopathic thrombocytopenic purpura, allogeneic bone marrow transplantation; Kawasaki disease and Guillain-Barré syndrome.1-3

There is some suggestion in the literature that IVIG may be beneficial in other conditions,1,2 particularly those in which alternative treatment modalities do not exist or are problematic, as with plasma exchange and long-term use of corticosteroids.

Use of IVIG in Children

IVIG Treatments for SJS / TEN

Toxic Epidermal Necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lyell’s syndrome) are now considered to be distinct clinical entities within a spectrum of adverse cutaneous drug reactions of increasing severity based on their surface of skin detachment. Within this spectrum, SJS which can be considered as a minor form of TEN is characterized by less than 10% body surface area of skin detachment, and an average reported mortality of 15%, whereas TEN is characterized by more than 30% skin detachment, and an average reported mortality 25-35%.

Both SJS and TEN are characterized morphologically by the rapid onset of keratinocyte cell death by apoptosis,

a process that results in the separation of the epidermis from the dermis. Recent evidence is supportive of a role for inflammatory cytokines and the death receptor Fas and its ligand FasL in the pathogenesis of keratinocyte apoptosis during TEN. This Fas-mediated keratinocyte apoptosis that is the last step culminating in epidermal detachment in TEN can be inhibited n vitro by antagonistic monoclonal antibodies to Fas, and by intravenous immunoglobulins (IVIG) which have been shown to contain natural anti-Fas antibodies. Consequently, over the last few years, numerous case reports and 9 non-controlled clinical studies containing 10 or more patients have analyzed the therapeutic effect of IVIG in TEN. Taken together, although each study has its potential biases, 7 of 9 such studies point towards a benefit of IVIG used at doses greater than 2 gkg on the mortality associated with TEN. These studies should serve as the basis for designing an appropriate prospective trial or for conducting a metaanalysis in the near future, in order to determine the therapeutic efficacy of IVIG in TEN.

Use of Intravenous Immunoglobulin

in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Seven Cases and Review of the Literature

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are the most severe cutaneous reactions that occur in children. Off-label use of human intravenous immunoglobulin (IVIG) has been reported in a number of autoimmune and cell-mediated blistering disorders of the skin, including severe cutaneous drug reactions.

We review 28 previous reports in which IVIG was used in pediatric patients with SJS and toxic epidermal necrolysis and discuss our experience in 7 children with SJS, in whom no new blisters developed within 24 to 48 hours after IVIG administration and rapid recovery ensued.

IVIG seems to be a useful and safe therapy for children with severe cutaneous drug reactions. Well-controlled, prospective, multicenter clinical trials are needed to determine optimal dosing guidelines and to compare the efficacy and safety of IVIG with other potentially effective modalities.