**10. IgG replacement therapy**

200 Immunodeficiency

exception may be re-immunization of otherwise immunologically normal patients who partially responded to PPV initially, with resulting titers slightly below protective levels.. Reimmunization of partial responders to PPV may result in protective antibody levels.

In contrast to the ineffectiveness of repeated PPV immunization, 80 to 90 percent of patients with classic PPV-SAD do have a serological response to the serotypes present in the conjugate vaccine that can be used to overcome the unresponsiveness to pure polysaccharides [56]. Conjugate vaccines were developed to immunize children younger than 2 years of age, as children below age 2 years typically demonstrate poor responses to polysaccharide antigens alone. Conjugation helps direct the immune response toward the immunogenic protein complexed to the polysaccharide antigen, thereby stimulating protective immune responses in those individuals. Therefore, it is not surprising that PPV-

Although most patients benefit from immunization with the conjugate vaccine by improving protection against common pneumococcal serotypes, none of the conjugate vaccines has all 23 serotypes present in the polysaccharide vaccine. This clinical improvement after a PCV immunization is notable because recurrent respiratory infections are caused by a much larger

If there is a serological response to the conjugate vaccine without clinical improvement, then the PPV-SAD persists and further treatment options need to be considered. In PPV-SAD patients who are clinically unresponsive to immunization with additional PCV, reimmunizing with PPV is generally ineffective if repeated within one year of the initial PPV vaccine. After a period of IgG therapy, many patients respond to an additional PPV dose with or without clinical improvement, so a second PPV dose should be given after

For patients with poor immunological memory (loss of antibody concentrations after an adequate initial response), immunization with a second dose of polysaccharide vaccine generally triggers a vigorous IgG antibody response. Further study is needed since this

If the frequency and severity of infections persists after additional immunization, antibiotic prophylaxis should be considered, especially in younger patients who will likely outgrow their selective antibody deficiency. When an oral antibiotic is considered for prophylaxis, treatment doses of trimetroprim-sulfa can be very effective. Prolonged daily use of topical mupirocin intranasally, for several months to a year, is a safe alternative treatment plan.

Appropriate antibiotic selection and duration for any febrile and/or purulent respiratory infection is important. Treatment with high doses of antibiotics for periods of at least 2 to 3 weeks is necessary. When antibiotic use alone improves the patient's quality of life and

nonresponders typically have a good serological response to PCV serotypes.

variety of pathogens than just the vaccine pneumococcal serotypes.

phenotype may not be attributable only to poor immunological memory.

prevents infectious complications, no additional treatment is needed.

completion of 1-2 years of IgG replacement therapy.

**9. Antibiotics** 

IgG replacement by the intravenous or the subcutaneous route is appropriate when the infection history is well documented, when immunizations have been utilized, and most of all, when proper antibiotic prophylaxis and treatment has been optimized. Patients with any form of SAD need decreased infections to improve quality of life and to prevent complications such hearing loss, sinus damage or bronchiectasis.

The recommended IgG dose is 400 to 600 mg/kg calculated on a monthly basis. ItgG can be given intravenously every four weeks or subcutaneously in divided doses one or twice weekly. Occasional patients require either higher doses if they have breakthrough infections or complications such as bronchiectasis.

When the severity of infections warrants the use of IgG replacement treatment, patients should be advised that treatment will be discontinued after a period of one to two years and the immune response will be reevaluated four to six months after discontinuation of IgG replacement. Whenever possible, the discontinuation of IVIG should be scheduled for during the spring or summer time when the incidence of infections typically decreases.

Four to six months after the IgG dose, a complete immunological evaluation of antibody mediated immunity should be performed. This evaluation includes an additional dose of PPV and measurement of antibodies 3 to 6 weeks after immunizations. Many children do not require further IgG replacement therapy, but some continue to have persistent infections and need continue replacement IgG therapy. These patients are likely to have additional immunological abnormalities that presently under evaluation. Patient management, IgG replacement therapy, and post treatment evaluation is best done by experts in the management of patients with all forms of primary immunodeficiency diseases.
