Common variable immunodeficiency (CVID), also known as common variable hypogammaglobulinemia, is a primary humoral immune deficiency, typically characterized by recurrent upper and lower respiratory tract infections due to bacterial and/or viral pathogens, defects in immune memory (in particular to polysaccharide antigens such as those found on pneumococcus), and an increased risk for autoimmune disease. Laboratory findings often include low total IgG (although this is not an absolute requirement), absent or inadequate vaccine responses, and low switched memory B cells on flow cytometry (CD27+ CD19+ IgM- IgD-).[1,2]
Our patient in this case had very high pneumococcal titers in three vaccine strains, which likely represented breakthrough infections (vaccine failures), as their values are too high for a 5-year-old boy. A more typical result at this age would show 7 to 10 serotypes reactive, with titers between 1-5 µg/mL. The loss of overall immunity, recurrent bacterial infections, and the slightly low total IgG indicate that CVID is the most likely diagnosis. CVID also presents with absent vaccine responses, most commonly to polysaccharide antigens; however, even highly immunogenic vaccines such as tetanus may be anergic in some individuals.
The diagnosis should be confirmed with either reboosting with pneumococcal vaccine or performing expanded flow-cytometry for switched memory B cells. Standardly, a normal primary vaccine response is a 4-fold increase in titers following immunization. Children who receive a full immunization schedule typically boost much higher, with postimmunization titers of 10-20 µg/mL or more, demonstrating a "memory" response. Failures to respond to live viral vaccines or proteins such as tetanus toxoid are much less common. At least two different vaccines from each category should be tested to reduce the risk for an incorrect diagnosis; however, if this finding is seen without vaccine titers in an immunized individual, the diagnosis of a primary immune deficiency is more likely.
Plain polysaccharide responses can occur from direct B-cell stimulation; however, responses are much lower in patients younger than 2 years. The conjugated polysaccharide vaccines used in infancy require a coordinated T-cell and B-cell response, and therefore a greater likelihood of vaccine failure as a result of relatively subtle immune defects. Respiratory pathogens, such as Haemophilus influenzae, pneumococcus, and streptococcus, have polysaccharide capsules; this helps explain the propensity for respiratory infections in children with CVID and other humoral immune deficiencies.
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Cite this: Recurrent Infections in a 5-Year-Old Boy - Medscape - Jul 30, 2018.