Relatives of patients with known genetic mutations causing hypogammaglobulinemia should be offered counseling followed by genetic testing if desired. Preimplantation genetic diagnosis has been offered in several cases where parents are known carriers. Screening of immunoglobulin levels in relatives of common variable immunodeficiency (CVID) patients demonstrates familial inheritance in 10% to 20% of CVID and IgA deficiency cases.[84]Hammarström L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000 May;120(2):225-31.
https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2249.2000.01131.x
http://www.ncbi.nlm.nih.gov/pubmed/10792368?tool=bestpractice.com
Secondary prevention also involves carefully monitoring patients likely to develop secondary hypogammaglobulinemia: for example, measuring immunoglobulins in patients with hematologic malignancy, or in those who are receiving chemotherapy or immunosuppressive therapy (e.g., rituximab). Rituximab is a B-cell depleting agent used in the treatment of hematologic malignancy and autoimmune disease. There is increasing recognition of rituximab-induced hypogammaglobulinemia usually following multiple doses of rituximab.[20]Levy R, Mahévas M, Galicier L, et al. Profound symptomatic hypogammaglobulinemia: a rare late complication after rituximab treatment for immune thrombocytopenia. Report of 3 cases and systematic review of the literature. Autoimmun Rev. 2014 Oct;13(10):1055-63.
http://www.ncbi.nlm.nih.gov/pubmed/25183241?tool=bestpractice.com
[21]Christou EA, Giardino G, Worth A, et al. Risk factors predisposing to the development of hypogammaglobulinemia and infections post-rituximab. Int Rev Immunol. 2017 Nov 2;36(6):352-9.
http://www.ncbi.nlm.nih.gov/pubmed/28800262?tool=bestpractice.com
[22]Khan DA. Hypersensitivity and immunologic reactions to biologics: opportunities for the allergist. Ann Allergy Asthma Immunol. 2016 Aug;117(2):115-20.
https://www.annallergy.org/article/S1081-1206(16)30263-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27499538?tool=bestpractice.com
[23]Ottaviano G, Marinoni M, Graziani S, et al. Rituximab unveils hypogammaglobulinemia and immunodeficiency in children with autoimmune cytopenia. J Allergy Clin Immunol Pract. 2020 Jan;8(1):273-82.
http://www.ncbi.nlm.nih.gov/pubmed/31377437?tool=bestpractice.com
Immunoglobulin levels should be monitored regularly (e.g., every 6 months) in patients receiving rituximab.[22]Khan DA. Hypersensitivity and immunologic reactions to biologics: opportunities for the allergist. Ann Allergy Asthma Immunol. 2016 Aug;117(2):115-20.
https://www.annallergy.org/article/S1081-1206(16)30263-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27499538?tool=bestpractice.com
[23]Ottaviano G, Marinoni M, Graziani S, et al. Rituximab unveils hypogammaglobulinemia and immunodeficiency in children with autoimmune cytopenia. J Allergy Clin Immunol Pract. 2020 Jan;8(1):273-82.
http://www.ncbi.nlm.nih.gov/pubmed/31377437?tool=bestpractice.com
[57]Barmettler S, Ong MS, Farmer JR, et al. Association of immunoglobulin levels, infectious risk, and mortality with rituximab and hypogammaglobulinemia. JAMA Netw Open. 2018 Nov 2;1(7):e184169.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2712179
http://www.ncbi.nlm.nih.gov/pubmed/30646343?tool=bestpractice.com
[58]Khojah AM, Miller ML, Klein-Gitelman MS, et al. Rituximab-associated hypogammaglobulinemia in pediatric patients with autoimmune diseases. Pediatr Rheumatol Online J. 2019 Aug 28;17(1):61.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712749
http://www.ncbi.nlm.nih.gov/pubmed/31462263?tool=bestpractice.com
Additionally, there is increasing data that pediatric patients treated with rituximab may be at higher risk for hypogammaglobulinemia and should be monitored.[23]Ottaviano G, Marinoni M, Graziani S, et al. Rituximab unveils hypogammaglobulinemia and immunodeficiency in children with autoimmune cytopenia. J Allergy Clin Immunol Pract. 2020 Jan;8(1):273-82.
http://www.ncbi.nlm.nih.gov/pubmed/31377437?tool=bestpractice.com
[58]Khojah AM, Miller ML, Klein-Gitelman MS, et al. Rituximab-associated hypogammaglobulinemia in pediatric patients with autoimmune diseases. Pediatr Rheumatol Online J. 2019 Aug 28;17(1):61.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712749
http://www.ncbi.nlm.nih.gov/pubmed/31462263?tool=bestpractice.com