Mild Hypogammaglobulinemia Can Be a Serious Condition

Abstract

Background: Most patients with primary antibody deficiency (PAD) suffer from less well-described and understood forms of hypogammaglobulinemia (unclassified primary antibody deficiency, unPAD). Because of the moderately decreased immunoglobulin levels compared to CVID, unPAD is generally considered to be clinically mild and not very relevant.Objective: To describe our cohort of—mainly—unPAD patients, and to analyze whether subgroups can be identified.Methods: Data were prospectively collected (February-2012 to June-2016) as part of a standardized, 1-day Care Pathway for suspected primary immunodeficiency. The TNO-AZL Questionnaire for Health-Related Quality of Life (HRQoL) was part of the pre-first-visit intake procedure.Results: Three hundred and twenty patients were referred to the Care Pathway. Data from 23/27 children and 99/113 adults who were diagnosed with PAD and gave informed consent were available for analysis. 89/99 adults had unPAD, the majority (74%) were female and 44% already showed bronchiectasis. HRQoL was significantly decreased in all domains, meaning that a lot of unPAD patients had to cope simultaneously with pain, negative feelings and impairments in cognition, home management tasks, sleep, social interaction, and work. The most prominently impaired HRQoL domain was vitality, indicating these patients feel extremely tired and worn out.Conclusion: These results highlight the need for more attention to the potential patient burden of unPADs. A larger cohort is needed to increase our understanding of unPADs and to analyze whether distinct subgroups can be identified. For now, it is important for the clinician to acknowledge the existence of unPAD and be aware of its potential consequences, in order to timely and appropriately manage its effects and complications.

The Natural History of Untreated Primary Hypogammaglobulinemia in Adults: Implications for the Diagnosis and Treatment of Common Variable Immunodeficiency Disorders (CVID)

“…Some studies have however shown impaired vaccine responses have correlated more closely with symptomatic state (31, 32). In one study, responses to tick-borne encephalitis vaccine was used as a neoantigen, responses which segregated with symptomatic state (31).…”

Focusing on Good Responders to Pneumococcal Polysaccharide Vaccination in General Hospital Patients Suspected for Immunodeficiency. A Decision Tree Based on the 23-Valent Pneumococcal IgG Assay

“…These patients generally present themselves in secondary care, where the pre-test probability for severe antibody deficiency is inherently low. However, even milder hypogammaglobulinemia can lead to serious problems, requiring adequate medical attention (14). These milder patients are often not recognized due to lack of available test facilities in secondary care, and reluctance to refer many patients to an immunologist.…”

Hypogammaglobulinemia: a diagnosis that must not be overlooked

“…Once patients are identified with serum immunoglobulin G (IgG) below the normal limit, the need for immunoglobulin replacement can be established. However, the finding of low IgG concentration itself, without a clinical manifestation, is still a subject of discussion regarding the appropriate treatment (25). In our study, there was marked variability in IgG levels at the time of diagnosis, from 30 to 563 mg/dL.…”

“…Immunoglobulin replacement is the basis of treatment for hypogammaglobulinemia, reducing sequelae from the respective immunological defect (4,25). The treatment can be administered intravenously or subcutaneously with variable doses, as determined by an individualized orientation.…”