Guidelines for Diagnosis and Management of Common Variable Immunodeficiency (CVID)

Diagnostic Criteria

A hallmark of CVID is a marked reduction in more than two immunoglobulin isotypes to levels below 50 % of the lower limit of normal; this laboratory pattern is required for diagnosis. [@2]
Functional antibody assessment is mandatory before confirming CVID: evaluate specific antibody responses to protein antigens such as tetanus and diphtheria toxoids. [@1][@3]
Functional antibody assessment also requires measuring the response to the 23‑valent pneumococcal polysaccharide vaccine both before immunization and 4 weeks afterward. [@1][@3]
In individuals older than 6 years, severe impairment of the pneumococcal polysaccharide response is defined as a concentration > 1.3 mg/mL for two or fewer serotypes. [@1][@4]
B‑cell flow cytometry must demonstrate abnormalities (e.g., altered memory B‑cell numbers or reduced isotype‑switched B cells) to support a CVID diagnosis. [@2]
Exclusion of secondary causes is essential: review medication history for agents such as antiepileptics, gold salts, penicillamine, hydroxychloroquine, and NSAIDs. [@3][@5]
Screen for HIV infection and other secondary immunodeficiencies. [@3]
Evaluate for malignancy, particularly lymphoma, as a potential secondary cause of hypogammaglobulinemia. [@2]
Measure serum total protein and albumin; low values suggest a secondary rather than primary hypogammaglobulinemia. [@1]

Initiate replacement when there is global failure of normal antibody production, evidenced by defective vaccine responses. [@2]
Start therapy in patients with recurrent sinopulmonary infections that adversely affect quality of life. [@3][@5]
Provide immunoglobulin replacement when end‑organ damage (e.g., bronchiectasis) is present. [@5]
Consider therapy if there is failure of or intolerance to aggressive antibiotic regimens. [@5]

Standard maintenance dosing of intravenous immunoglobulin (IVIG) is 400–600 mg/kg administered every 3–4 weeks. [@2]
(Subcutaneous immunoglobulin dosing and conversion formulas are described in other sources but are not cited in the current references.)

Prior to initiating therapy, ensure exclusion of secondary causes and confirm defective vaccine responses to avoid unnecessary treatment. [@2]
Ongoing clinical surveillance is recommended because some patients with initial IgG subclass deficiencies may progress to full CVID over time. [@3][@5]
Conversely, infection frequency and severity may decrease despite persistent immunologic abnormalities, underscoring the need for individualized follow‑up. [@5]