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Should one treat patients with asymptomatic (infrequent infections) CVID (or hypogammaglobulinemia with IgG subclass deficiency) with Ig replacement?


The short answer is no, I would not recommend gamma globulin replacement in an asymptomatic individual with hypogammaglobulinemia. Hypogammaglobulinemia is not equivalent to common variable immunodeficiency or IgG subclass deficiency or functional antibody deficiency (1). The diagnosis of these conditions requires more information than the description ‘hypogammaglobulinemia’. I would consider in an asymptomatic individual monitoring of the IgG with time. Depending on the degree of hypogammaglobulinemia I would also consider measuring all isotypes (i.e. IgG, IgM, IgA), checking for lymphopenia, considering immunofixation for monoclonal gammopathy, and assessing ability to make specific antibody to proteins (e.g. tetanus, diphtheria) and B lymphocyte antigens such as polysaccharide (e.g. unconjugated pneumococcal vaccine). The results would influence how closely I monitor the patient and how I counsel with regards to risk of infection in the future. Subclass deficiency does not require treatment unless specific antibody response is impaired and the subject has increased infections, usually respiratory. I would also suggest reviewing medications currently utilized and consider seeking input from other treating physicians about discontinuing, if possible, drugs such phenytoin, carbamazepine, or valproic acid (2).

1. Filion, Charles A., et al. "Differentiation of common variable immunodeficiency from IgG deficiency." The Journal of Allergy and Clinical Immunology: In Practice 7.4 (2019): 1277-1284.
2. Dhalla, Fatima, and Siraj A. Misbah. "Secondary antibody deficiencies." Current opinion in allergy and clinical immunology 15.6 (2015): 505-513.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI

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