Differential diagnosis in hypogammaglobulinemia

Hypogammaglobulinemias are characterized by low or deficient levels of any of the immunoglobulins (IgG, IgA, IgM, IgE, and IgG subclasses). This condition repre- sents a diagnostic challenge for clinicians, due to its association with many patho- logical entities with different manifestations and outcomes. At the initial evaluation, several factors should be considered to correctly recognize the possible cause of hypogammaglobulinemia, including age of onset, sex, number and type immuno- globulin class involved, vaccine responses, clinical manifestations, comorbidities, and medications. Clinician must have a high level of suspicion for antibody defi- ciency for all patients when a serum hypogammaglobulinemia is evident. In the registry of European Society for Immunodeficiencies (ESID), the vast majority of cases of antibody disorders involve a hypogammaglobulinemia, including common variable immunodeficiency disorder (CVID), the most reported one. As described in Chap. 3, CVID is characterized by marked decrease of IgG and IgA serum levels, recurrent respiratory infections and/or autoimmune features, and impaired vaccine response in association with pathological B subset immunophenotype. Some patients with a low IgG level and impaired vaccine responses may not fulfill criteria for CVID because IgA or IgM level is not low. This form of hypogammaglobu- linemia with antibody deficiency should be classified as “unspecified IgG defi- ciency” or “unspecified hypogammaglobulinemia”