Differential Diagnosis in Hypogammaglobulinemia

Abstract

Hypogammaglobulinemia is defined as an impaired production of antibodies. This condition represents a diagnostic challenge for clinicians, due to its association with many pathological entities with different manifestations and outcomes. Primary hypogammaglobulinemia is caused by defects in B-cell number and maturation, reduced survival and activation of B cells, and faulty interaction between B and T cells and is commonly observed in many primary immunodeficiencies. However, hypogammaglobulinemia secondary to cancer, chemotherapy, immunosuppressive therapy, chromosomal alterations, and protein-losing diseases is a widely recognized condition. The clinical relevance of secondary hypogammaglobulinemias has been increasingly recognized. Differential diagnosis could be puzzling because of similar clinical aspects in primary and secondary forms of hypogammaglobulinemias. Thus, for all patients with a low immunoglobulin serum level at the initial evaluation, defined causes of secondary hypogammaglobulinemias should be extensively ruled out. In particular, B-cell malignancies (mainly chronic lymphocytic leukemia) and plasma cell dyscrasias should be excluded in patients with low immunoglobulin serum levels.