Primary antibody immunodeficiency with hypogammaglobulinemia (low IgG plus low IgA/IgM) causing recurrent infections and immune dysregulation (autoimmunity).
Most common symptomatic primary immunodeficiency; leads to recurrent sinopulmonary infections, chronic lung damage (bronchiectasis), frequent autoimmune diseases (e.g., ITP, hemolytic anemia), and increased lymphoma risk.
Usually presents in teens or adults (but sometimes after age 4); recurrent otitis, sinusitis, pneumonia are typical. Chronic diarrhea (often from Giardia) is also common.
Autoimmune complications (e.g., cytopenias like ITP or AIHA, thyroid disease) and non-caseating granulomas (sarcoid-like lung or lymphoid lesions) can occur, adding to the variable features.
Labs: ↓ IgG (with ↓IgA and/or ↓IgM) and poor vaccine antibody response (no protective titers after immunizations). B cells are present (normal or low-normal count, unlike XLA).
Suspect CVID in older children or adults with recurrent bacterial infections affecting ears, sinuses, lungs (and sometimes chronic diarrhea).
First, check quantitative immunoglobulin levels: significantly low IgG (≥2 SD below normal for age) with low IgA and/or IgM confirms hypogammaglobulinemia.
Test antibody function: measure specific antibody titers after vaccines (e.g., pneumococcal vaccine) – CVID patients show poor or absent response despite vaccination.
Exclude secondary causes of low immunoglobulins: test for HIV; evaluate for protein loss (nephrotic syndrome or protein-losing enteropathy); review medications (e.g., immunosuppressants, anti-seizure drugs); rule out lymphoid malignancy (CLL, myeloma).
Distinguish from other primary immunodeficiencies: CVID has normal B-cell numbers and later onset in both sexes (vs. X-linked agammaglobulinemia – no B cells, infant boys; vs. hyper-IgM – high IgM; vs. SCID – T-cell deficits and infant onset).
Condition
Distinguishing Feature
X-linked agammaglobulinemia (Bruton)
Male infant with recurrent infections starting ~6mo; no B cells on flow cytometry, all Ig classes low.
Selective IgA deficiency
IgA low, but IgG/IgM normal; may have recurrent mucosal infections but often asymptomatic; most common immunoglobulin deficiency.
Hyper-IgM syndrome
High IgM, very low IgG/IgA; often X-linked (CD40L defect); presents in infancy with severe sinopulmonary and opportunistic infections.
Immunoglobulin replacement therapy for life (regular IVIG or SCIG infusions) to restore IgG levels and reduce infections.
Aggressive treatment of infections (antibiotics); consider prophylactic antibiotics if needed for recurrent bacterial infections.
No live vaccines (they often won't mount response; use inactivated vaccines in close contacts instead for herd protection).
Monitor for complications: manage autoimmune disorders (e.g., IVIG also helps ITP), screen for lymphoma if persistent lymphadenopathy or organ enlargement, and perform lung imaging/PFTs if chronic respiratory symptoms (for bronchiectasis or GLILD).
Remember CVID as Common & Variable: the most common clinically significant immunodeficiency with highly variable presentation (infections + autoimmunity + granulomas).
Unexplained weight loss, chronic diarrhea, or abdominal pain in CVID → evaluate for GI involvement (sprue-like enteropathy) or GI lymphoma.
Recurrent pneumonia in CVID patient → get imaging; early bronchiectasis can develop, requiring pulmonary care (airway clearance, possibly prophylactic antibiotics).
Hepatosplenomegaly or lymph node enlargement in CVID → consider lymphoma (much higher risk in CVID) and pursue appropriate workup (imaging/biopsy).
Recurrent respiratory or GI infections in child >4 or adult → suspect CVID (check immunoglobulin levels).
Low IgG (and low IgA/IgM) on two occasions → proceed to functional antibody testing (vaccine titers).
Confirm poor antibody response to vaccines or isohemagglutinins → supports CVID diagnosis.
Exclude secondary immunodeficiencies (HIV, protein loss, medications, malignancy) and other primary IDs (if male infant with no B cells, that's XLA; if severe T-cell defects, think SCID).
Diagnosis of exclusion confirmed → begin IVIG therapy and routine monitoring (infections, autoimmunity, malignancy surveillance).
Young adult with recurrent sinus infections, pneumonias, and chronic diarrhea (Giardia) who has low immunoglobulin levels → Common variable immunodeficiency.
10‑year‑old girl with a history of multiple pneumonias and otitis media, plus an episode of autoimmune thrombocytopenia, found to have low IgG and IgA levels → CVID (distinguish from XLA by female sex and presence of B cells).
Adult CVID patient with chronic cough and lung nodules on CT is found to have non-caseating granulomas (GLILD) → indicates CVID-related granulomatous disease (not sarcoidosis).
Case 1
A 28‑year‑old man has a history of recurrent sinus infections, two pneumonias, and chronic diarrhea due to Giardia.
Case 2
A 10‑year‑old female with multiple episodes of pneumonia and otitis media is evaluated for immune deficiency. She also had immune thrombocytopenic purpura (ITP) last year.
Intravenous immunoglobulin (IVIG) infusion being administered to a CVID patient.
