Application of diagnostic and treatment criteria for common variable immunodeficiency disorder

ABSTRACT

Common variable immunodeficiency disorder (CVID) is the most frequent symptomatic primary immune deficiency disorder in adults. It probably comprises a spectrum of polygenic disorders, with hypogammaglobulinemia being the overarching feature. While the majority of patients with CVID can be identified with relative ease, a significant proportion can present with minimal symptoms in spite of profound laboratory abnormalities. Here we discuss three patients who were presented to the Auckland Hospital immunoglobulin treatment committee to determine if they qualified for immunoglobulin replacement. Two were asymptomatic with profound laboratory abnormalities while the third patient was severely ill with extensive bronchiectasis. The third patient had less severe laboratory abnormalities compared with the two asymptomatic patients. We have applied four sets of published diagnostic and treatment criteria to these patients to compare their clinical utility. We have chosen these patients from the broad phenotypic spectrum of CVID, as this often illustrates differences in diagnostic and treatment criteria.

KEYWORDS:

• Common Variable Immunodeficiency
• diagnostic criteria
• HGUS

Acknowledgments

We thank our patients for participating in our studies for the benefit of others. We hope our studies will assist colleagues when facing difficult and complex medical decisions, as illustrated here. We thank our colleagues from around the world for their valuable comments.

Financial & competing interests disclosure

R Ameratunga has received an unrestricted educational grant from Octapharma for studies on CVID patients. We thank LabPlus management for supporting our studies as well the Auckland Medical Research Foundation, A+ Trust for grant support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• It is very important for patients with suspected CVID to be thoroughly reviewed as there may be subclinical lung disease, as seen in patient 2.

• In spite of profound hypogammaglobulinemia, some patients can remain very well. However, in general, patients with severe hypogammaglobulinemia should be treated with immunoglobulin, as they are at risk of severe sepsis, meningitis, etc.

• Diagnostic criteria will remain important for patients who do not have a monogenic explanation for their hypogammaglobulinemia.

• The heavy emphasis on vaccine responses with the previous ESID/PAGID (1999) criteria is problematic.

• The Ameratunga et al. criteria are similar to the revised ESID registry (2014) criteria.

• The Ameratunga et al. and Agarwal and Cunningham-Rundles criteria can assist with decisions to treat with IVIG/SCIG.

• Construction of a template (Table 5) based on diagnostic and treatment criteria (Tables 1–4) will assist diagnostic and treatment decisions.

• It will be important to validate these criteria with larger cohorts of patients from around the world.

• Long-term studies will ultimately establish the sensitivity and specificity of these criteria, which may differ in cohorts from around world.

• These patients should be under the care of experienced immunologists as clinical judgment is paramount in management, as illustrated by these cases.