Secondary Hypogammaglobulinemia

Secondary hypogammaglobulinemia is acquired reduction in total immunoglobulin (IgG <600 mg/dL or below age-adjusted normal) and/or specific antibody response, distinct from primary immunodeficiencies. The leading drug causes are anti-CD20 monoclonal antibodies (rituximab, ocrelizumab, ofatumumab), anti-CD38 (daratumumab), corticosteroids, anti-epileptic drugs (phenytoin, carbamazepine), and chemotherapy.

Disease-related causes include chronic lymphocytic leukemia, multiple myeloma, non-Hodgkin lymphoma, thymoma (Good syndrome), nephrotic syndrome, protein-losing enteropathy, severe burns, and post-hematopoietic stem cell transplantation. The clinical phenotype mirrors primary hypogammaglobulinemia: recurrent sinopulmonary infections, encapsulated bacterial bronchopneumonia, otitis, sinusitis, and gastrointestinal infections (Giardia, Campylobacter).

Workup includes quantitative serum immunoglobulins (IgG, IgA, IgM, IgG subclasses), specific antibody titers to vaccine antigens (tetanus, pneumococcus, Haemophilus), B-cell flow cytometry, and screening for underlying malignancy (CT chest-abdomen, paraprotein, free light chains). Management combines causative therapy when feasible (drug holiday, treat malignancy), antibiotic prophylaxis with cotrimoxazole or azithromycin for recurrent infections, vaccination with non-live vaccines (often poor response), and IgG replacement therapy (IVIG 0.4-0.6 g/kg every 3-4 weeks or SCIG 100-200 mg/kg weekly) for symptomatic patients with documented infection susceptibility.