Original Article

CME Article: Common Variable Immune Deficiency: An Outpatient Experience

Authors: Carmen Popa, MD, Robert Fischer, MBBS, Shamai Kurbitaeva, MD, Keyvan Ravakhah, MD


Objectives: Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies encountered by physicians, yet it is still poorly described and vastly underdiagnosed and underreported. It is characterized by low levels of immunoglobulins IgG, IgM, and IgA, recurrent infections, and an increased incidence of autoimmune conditions and malignancies. Diverse clinical presentation, poor understanding of its true prevalence, and the daunting, rarely ordered, diagnostic testing make this disease incredibly difficult to diagnose in a primary care setting. Our objectives in this study were to establish a simple marker that can be used in a primary care setting to raise suspicion of CVID and prompt further diagnostic testing and to demonstrate that the true prevalence of CVID is much higher than previously reported.

Methods: Data on 441 patients who underwent Ig electrophoresis testing during a 4-year period were analyzed retrospectively for the presence of hypogammaglobulinemia and number of clinic visits for infectious processes.

Results: The average number of clinic visits before testing in patients with no identified antibody deficiency was 1.89 and in patients with any deficiency 2.22. The odds ratio for each additional visit was 1.089, which was not statistically significant (P = 0.103). When the data were recoded to be capped at 6 clinic visits, the odds ratio for each visit up to 6 was 1.119, which was marginally significant (P = 0.058).

Conclusions: Patients with Ig deficiencies tend to have a higher number of office visits related to infectious processes. This difference, however, was not statistically significant in our study, likely because of the small number of participants. Our study also demonstrated that the prevalence of CVID is likely much higher than currently reported, and it highlights the difficulties related to the convoluted diagnostic process of this disease.
Posted in: Allergy and Immunology7 Autoimmune Systemic Disorders2

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Barilla-LaBarca ML, Rodriguez M, Connors K, et al. Common variable immunodeficiency: a standardized patient case for second-year medical students. MedEdPORTAL 2019;15:10837.
2. Gathmann B, Mahlaoui N, Gérard L, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol 2014;134:116–126.
3. Park MA, Li JT, Hagan JB, et al. Common variable immunodeficiency: a new look at an old disease. Lancet 2008;372:489–502.
4. Jolles S. The variable in common variable immunodeficiency: a disease of complex phenotypes. J Allergy Clin Immunol Pract 2013;1:545–557.
5. Ghafoor A, Joseph SM. Making a diagnosis of common variable immunodeficiency: a review. Cureus 2020;12:e6711.
6. Moazzami B, Mohayeji Nasrabadi MA, Abolhassani H, et al. Comprehensive assessment of respiratory complications in patients with common variable immunodeficiency. Ann Allergy Asthma Immunol 2020;124:505–511.e3.
7. Abbott JK, Gelfand EW. Common variable immunodeficiency: diagnosis, management, and treatment. Immunol Allergy Clin North Am 2015;35:637–658.
8. Cunningham-Rundles C, Maglione PJ. Common variable immunodeficiency. J Allergy Clin Immunol 2012;129:1425–1426.e3.
9. Sperlich JM, Grimbacher B, Workman S, et al. Respiratory infections and antibiotic usage in common variable immunodeficiency. J Allergy Clin Immunol Pract 2018;6:159–168.e3.
10. Erdem SB, Gulez N, Genel F, et al. Characteristics of the patients followed with the diagnosis of common variable immunodeficiency and the complications. Cent Eur J Immunol 2019;44:119–126.
11. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 1999;93:190–197.
12. Ameratunga R, Woon S-T, Gillis D, et al. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol 2013; 174:203–211.
13. Chapel H, Charlotte Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol 2009;145:709–727.
14. Ritchie RF, Palomaki GE, Neveux LM, et al. Reference distributions for immunoglobulins A, G, and M: a practical, simple, and clinically relevant approach in a large cohort. J Clin Lab Anal 1998;12:363–370.
15. Koopmans W, Woon S-T, Brooks AES, et al. Clinical variability of family members with the C104R mutation in transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). J Clin Immunol 2013; 33:68–73.
16. Goldacker S, Draeger R, Warnatz K, et al. Active vaccination in patients with common variable immunodeficiency (CVID).Clin Immunol 2007;124:294–303.
17. Thierry-Carstensen B, Jordan K, Hylland Uhlving H, et al. A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults. Vaccine 2012;30:5464–5471.
18. Hawdon N, Nix EB, Tsang RSW, et al. Immune response to Haemophilus influenzae type b vaccination in patients with chronic renal failure. Clin Vaccine Immunol 2012;19:967–969.
19. Lee H, Nahm MH, Kim K-H. The effect of age on the response to the pneumococcal polysaccharide vaccine. BMC Infect Dis 2010;10:60.
20. Seppänen M, Aghamohammadi A, Rezaei N. Is there a need to redefine the diagnostic criteria for common variable immunodeficiency? Expert Rev Clin Immunol 2014;10:1–5.