If and When to Consider Prophylactic Immunoglobulin Replacement Therapy in Secondary Hypogammaglobulinemia

Secondary hypogammaglobulinemia (SHG), or decreased IgG levels due to reduced production or increased loss caused by medications or underlying conditions, can be associated with increased infection risk. Although immunoglobulin replacement therapy (IgRT) is generally accepted as a strategy to help prevent recurrent bacterial infections in SHG, controversy exists as to whether it should be initiated to prevent the first occurrence of infection. This question has been raised particularly in the setting of anti-CD20 therapy, solid organ transplant, and B-cell malignancies and their treatments once IgG levels fall below 300 to 400 mg/dL. This article reviews the evidence for and against initiating IgRT in these settings, as well as associated considerations for evaluation and monitoring. Although it is relatively clear that infection risk increases with decreasing IgG levels, the exact contribution of SHG to overall infection risk and the protective benefit of IgRT in the absence of infections remain unclear. In the absence of clear consensus, shared decision-making is often needed to determine if and when to initiate IgRT.