State-of-the-art diagnostic evaluation of common variable immunodeficiency

Abstract

Objective: To summarize the current understanding of diagnostic and postdiagnostic evaluation of common variable immunodeficiency (CVID).

Data sources: PubMed Central database.

Study selections: Original research articles and review articles from 2015 to 2020 including seminal articles that shaped the diagnostic and postdiagnostic evaluation of CVID were incorporated. This work focuses on initial diagnosis of CVID, genetic evaluations, and postdiagnostic assessment of respiratory, gastrointestinal, and hepatobiliary diseases including spleen and lymph node enlargement.

Results: CVID presents not only with frequent infections but also with noninfectious complications such as autoimmunity, gastrointestinal disease, chronic lung disease, granulomas, liver disease, lymphoid hyperplasia, splenomegaly, or malignancy. The risk of morbidity and mortality is higher in patients with CVID and noninfectious complications. Detailed diagnostic approaches, which may incorporate genetic testing, can aid characterization of individual CVID cases and shape treatment in some instances. Moreover, continued evaluation after CVID diagnosis is key to optimal management of this complex disorder. These postdiagnostic evaluations include pulmonary function testing, radiologic studies, and laboratory evaluations that may be conducted at frequencies determined by disease activity.

Conclusion: Although the diagnosis can be achieved similarly in all patients with CVID, those with noninfectious complications have distinct concerns during clinical evaluation. State-of-the-art workup of CVID with noninfectious complications typically includes genetic analysis, which may shape precision therapy, and thoughtful application of postdiagnostic tests that monitor the presence and progression of disease in the myriad of tissues that may be affected. Even with recent advancements, knowledge gaps in diagnosis, prognosis, and treatment of CVID persist, and continued research efforts are needed.

Figure 1.

Commonality and differences in key aspects of CVID diagnosis between ESID and ICON. ESID = European society for immunodeficiencies; ICON = international consensus document.

Figure 2.

Proposed strategy for clinical evaluation of CVID.