Comparison of diagnostic criteria for common variable immunodeficiency disorder

Abstract

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immune deficiency condition in adults. The genetic basis for the condition is not known and no single clinical feature or laboratory test can establish the diagnosis; it has been a diagnosis of exclusion. In areas of uncertainty, diagnostic criteria can provide valuable clinical information. Here, we compare the revised European society of immune deficiencies (ESID) registry (2014) criteria with the diagnostic criteria of Ameratunga et al. (2013) and the original ESID/pan American group for immune deficiency (ESID/PAGID 1999) criteria. The ESID/PAGID (1999) criteria either require absent isohemagglutinins or impaired vaccine responses to establish the diagnosis in patients with primary hypogammaglobulinemia. Although commonly encountered, infective and autoimmune sequelae of CVID were not part of the original ESID/PAGID (1999) criteria. Also excluded were a series of characteristic laboratory and histological abnormalities, which are useful when making the diagnosis. The diagnostic criteria of Ameratunga et al. (2013) for CVID are based on these markers. The revised ESID registry (2014) criteria for CVID require the presence of symptoms as well as laboratory abnormalities to establish the diagnosis. Once validated, criteria for CVID will improve diagnostic precision and will result in more equitable and judicious use of intravenous or subcutaneous immunoglobulin therapy.

Keywords: HGUS; common variable immunodeficiency; diagnostic criteria.

Figure 1

Treatment algorithm for CVID (21). Patients must meet all major criteria in category A for consideration of CVID. Category B confirms the presence of symptoms indicating immune system failure (ISF). To have probable CVID, patients must also have supportive laboratory evidence of immune system dysfunction (category C) or characteristic histological lesions of CVID (category D). Patients with mild hypogammaglobulinemia (IgG > 5 g/l) are termed hypogammaglobulinemia of uncertain significance (HGUS). Patients meeting category A criteria but not other criteria are deemed to have possible CVID. Most patients with probable CVID are likely to require IVIG/SCIG. Some patients with possible CVID who have profound hypogammaglobulinemia will require IVIG/SCIG but most patients with HGUS are unlikely to need IVIG/SCIG replacement.