Diagnostic Criteria for Common Variable Immunodeficiency (CVID): Probable and Possible Diagnosis

The diagnostic criteria are divided into three categories: definitive, probable, and possible. There are no criteria for definitive diagnosis of Common Variable Immunodeficiency (CVID) at this time.

To guard against the inclusion of patients who have polymorphic variants in the genes associated with immunodeficiency and to specify the clinical or laboratory finding that is most consistently abnormal in a particular disorder, the patient must fulfill an inclusion criterion that is characteristic of the disorder.

Definitive diagnosis

Patients with a definitive diagnosis are assumed to have a greater than 98% probability that in 20 years they will still be given the same diagnosis. Mutation detection is the most reliable method of making a diagnosis but a single mutation is rarely found in CVID.

Probable diagnosis

Patients with a probable diagnosis are those with all of the clinical and laboratory characteristics of a particular disorder but who do not have a documented abnormality in the gene, the mRNA, or the protein that is known to be abnormal in the disorder. They are assumed to have a greater than 85% probability that in 20 years they will be given the same diagnosis.

Probable diagnosis of CVID:

Male or female patient who has a marked decrease (at least 2 SD below the mean for age) in serum IgG AND IgA and fulfills all of the following criteria:

1. Onset of immunodeficiency at greater than 2 years of age.

2. Absent isohemagglutinins and/or poor response to vaccines.

3. Defined causes of hypogammaglobulinemia have been excluded

Possible diagnosis

Patients with a possible diagnosis are those that have some but not all of the characteristic clinical or laboratory findings of a particular disorder.

Possible diagnosis if CVID:

Male or female patient who has a marked decrease (at least 2 SD below the mean for age) in one of the major isotypes (IgM, IgG, and IgA) and fulfills all of the following criteria:

1. Onset of immunodeficiency at greater than 2 years of age.

2. Absent isohemagglutinins and/or poor response to vaccines.

3. Defined causes of hypogammaglobulinemia have been excluded

Clinical features of CVID

Most patients with CVID are diagnosed with immunodeficiency in the second, third, or fourth decade of life, after they have had several pneumonias; however, children and older adults may be affected.

Viral, fungal, and parasitic infections as well as bacterial infections may be found.

The serum concentration of IgM is normal in about half of the patients.

Abnormalities in T cell numbers or function are common. The majority of patients have normal numbers of B cells; however, some have low or absent B cells.

Approximately 50% of patients have autoimmune manifestations. There is an increased risk of malignancy.

Differential diagnosis of hypogammaglobulinemia includes drug-induced, for example secondary to glucocorticoids (steroids).



Typical pattern of immunoglobulin levels (IgG, IgA, IgM) in humoral immunodeficiency. Click here to enlarge the table.

References

Diagnostic Criteria for Primary Immunodeficiencies. Mary Ellen Conley, Luigi D. Notarangelo, and Amos Etzioni Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical Immunology, Vol. 93, No. 3, December, pp. 190–197, 1999.

Recognizing Primary Immune Deficiency in Clinical Practice. Clinical and Vaccine Immunology, March 2006, p. 329-332, Vol. 13, No. 3.