Update on Systemic Therapies for Atopic Dermatitis
Update on Systemic Therapies for Atopic Dermatitis
IVIG is FDA approved for the treatment of pediatric HIV infections, chronic lymphocytic leukemia, idiopathic thrombocytopenic purpura, Kawasaki's disease, primary immunodeficiencies, chronic inflammatory demyelinating polyneuropathy, and kidney transplantation when there is a high likelihood of rejection (ABO incompatibility or a recipient with markedly elevated antibody titer). There are a number of theories proposed for IVIGs mechanism of action in these diseases. These include competing for Fc receptors of macrophages and other antigen presenting cells, altering production of various cytokines, neutralization of pathogens that exacerbate or initiate the disease process, neutralization of autoantibodies, increasing the turnover rate of antibodies, decreasing B and T cell proliferation, increasing the binding affinity of glucocorticoid receptors, inhibiting complement-mediated damage, inhibition of Fas-mediated cell death, and binding of cellular adhesion molecules. Treatment of severe refractory atopic dermatitis with IVIG has yielded conflicting results and therefore it is not widely used. Nevertheless, IVIG has been shown to contain high concentrations of staphylococcal toxin-specific neutralizing antibodies that can inhibit the in-vitro activation of T cells by staphylococcal toxins. In 2011, a small case series of four highly allergic atopic dermatitis patients (three pediatric/one adult) demonstrated significant improvement with monthly infusions of IVIG (0.5–1.0 g/kg/dose), based on SCORAD assessments, but this benefit was only observed in pediatric cases. This is consistent with the prior literature that suggests this treatment is most effective in pediatric cases as either a stand-alone treatment or more commonly as add-on therapy.
In a RCT of IVIG (2.0 g/kg/month for 3 months) to treat moderate-to-severe pediatric atopic dermatitis patients (n = 40), a statistically significant reduction in SCORAD was observed after three infusions which was even more impressive by 3 months after discontinuing treatment. Unfortunately, disease relapse was observed by 6 months after discontinuing treatment. These improvements were accompanied by reductions in serum IL-5/IFNγ ratio, soluble ICAM-1, and eosinophil cationic protein levels, but no changes were noted in total eosinophil counts or serum total IgE values. Additional RCT are needed to determine the optimum dose of IVIG for clearance and maintenance and the patient population most likely to respond to this therapy. As IVIG is an expensive treatment, with an unclear mechanism of action, it should generally be relegated to a last resort treatment approach and probably only in pediatric atopic dermatitis patients.
Intravenous Immunoglobulin
IVIG is FDA approved for the treatment of pediatric HIV infections, chronic lymphocytic leukemia, idiopathic thrombocytopenic purpura, Kawasaki's disease, primary immunodeficiencies, chronic inflammatory demyelinating polyneuropathy, and kidney transplantation when there is a high likelihood of rejection (ABO incompatibility or a recipient with markedly elevated antibody titer). There are a number of theories proposed for IVIGs mechanism of action in these diseases. These include competing for Fc receptors of macrophages and other antigen presenting cells, altering production of various cytokines, neutralization of pathogens that exacerbate or initiate the disease process, neutralization of autoantibodies, increasing the turnover rate of antibodies, decreasing B and T cell proliferation, increasing the binding affinity of glucocorticoid receptors, inhibiting complement-mediated damage, inhibition of Fas-mediated cell death, and binding of cellular adhesion molecules. Treatment of severe refractory atopic dermatitis with IVIG has yielded conflicting results and therefore it is not widely used. Nevertheless, IVIG has been shown to contain high concentrations of staphylococcal toxin-specific neutralizing antibodies that can inhibit the in-vitro activation of T cells by staphylococcal toxins. In 2011, a small case series of four highly allergic atopic dermatitis patients (three pediatric/one adult) demonstrated significant improvement with monthly infusions of IVIG (0.5–1.0 g/kg/dose), based on SCORAD assessments, but this benefit was only observed in pediatric cases. This is consistent with the prior literature that suggests this treatment is most effective in pediatric cases as either a stand-alone treatment or more commonly as add-on therapy.
In a RCT of IVIG (2.0 g/kg/month for 3 months) to treat moderate-to-severe pediatric atopic dermatitis patients (n = 40), a statistically significant reduction in SCORAD was observed after three infusions which was even more impressive by 3 months after discontinuing treatment. Unfortunately, disease relapse was observed by 6 months after discontinuing treatment. These improvements were accompanied by reductions in serum IL-5/IFNγ ratio, soluble ICAM-1, and eosinophil cationic protein levels, but no changes were noted in total eosinophil counts or serum total IgE values. Additional RCT are needed to determine the optimum dose of IVIG for clearance and maintenance and the patient population most likely to respond to this therapy. As IVIG is an expensive treatment, with an unclear mechanism of action, it should generally be relegated to a last resort treatment approach and probably only in pediatric atopic dermatitis patients.
