A 14-year-old boy is brought to the clinic due to severe left ear pain. Medical history includes several episodes of acute otitis media as a toddler; each infection resolved promptly with antibiotics. Over the past 3 years, the patient has developed recurrent acute otitis media, often complicated by sinusitis. Last year, he missed 2 weeks of school due to an episode of pneumonia. Vital signs are unremarkable. Examination shows an erythematous and bulging left tympanic membrane. Immunoglobulin testing reveals:
| IgM | 40 mg/dL (normal: 38-266) |
| IgG | 258 mg/dL (normal: 768-1728) |
| IgA | 28 mg/dL (normal: 99-396) |
Vaccinations are up to date, but vaccine titers for tetanus, diphtheria, and pneumococcus are low. Which of the following defects is most likely present in this patient?
Primary immunodeficiency syndromes | ||||
Classifications | Age of onset | Key features | Laboratory findings | Examples |
B-cell disorders | Variable (>4-6 months) |
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T-cell (& combined B- & T-cell) disorders | Early (<4-6 months) |
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Phagocyte disorders | Early (childhood) |
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Complement disorders | Variable |
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*Only in X-linked agammaglobulinemia. **Only in chronic granulomatous disease (eg, Staphylococcus aureus, Burkholderia, Serratia, Aspergillus, Nocardia). Ig = immunoglobulin. | ||||
This patient with recurrent sinus and ear infections has low immunoglobulin levels and a decreased antibody response to vaccines. These findings are concerning for a primary humoral immunodeficiency such as common variable immunodeficiency (CVID). CVID is caused by impaired differentiation of B cells into plasma cells, which results in decreased production of various immunoglobulins.
CVID commonly presents in early adulthood (age 20-40) or adolescence (around puberty) with recurrent sinopulmonary infections, typically caused by encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae) because antibody opsonization is required for clearance of these organisms. Recurrent gastrointestinal infections (eg, Salmonella, Campylobacter, Giardia) can also occur due to low IgA levels. In addition, patients may have associated atopic (eg, asthma, eczema) or autoimmune (eg, rheumatoid arthritis) conditions.
Immunoglobulin profile in patients with CVID reveals low IgG as well as low IgA and/or IgM. Antibody responses to vaccines (ie, vaccine titers) are also low. Complete blood count would show a normal amount of white blood cells. Treatment is immunoglobulin replacement therapy.
(Choice A) X-linked agammaglobulinemia (XLA) is characterized by absent B-cell production due to a defect in pre–B-cell maturation in the bone marrow. All immunoglobulin levels and vaccine titers are markedly low or absent. However, presentation is typically in infant boys after maternally derived IgG wanes (age 4-6 months), and there is often a family history of males with recurrent hospitalizations. Although this adolescent patient had ear infections as a toddler, these are common in any toddler and resolved quickly with antibiotics; furthermore, the patient had no other infections during most of his childhood, which would be unusual for XLA and makes CVID more likely.
(Choice B) Classic presentation of terminal complement deficiency is recurrent Neisseria infections. Immunoglobulin levels and vaccine titers would be normal.
(Choice D) Because helper T cells play a role in B-cell activation, patients with T-cell deficiency (eg, severe combined immunodeficiency) may have decreased antibody production in addition to impaired cell-mediated immunity. Unlike in this patient, severe bacterial, viral, and fungal infections would begin in early infancy.
(Choice E) Leukocyte adhesion deficiency is characterized by impaired neutrophil chemotaxis, leading to frequent skin and respiratory infections. Immunoglobulin levels and vaccine titers would not be affected.
Educational objective:
Common variable immunodeficiency is characterized by decreased immunoglobulin production due to impaired differentiation of B cells into plasma cells. Patients typically develop recurrent sinopulmonary infections after puberty and have low IgG plus low IgA and/or IgM, as well as decreased antibody response to vaccines.