Hypogammaglobulinemia: a diagnosis that must not be overlooked

Abstract

Humoral immunological defects are frequent and important causes of hypogammaglobulinemia, leading to recurrent infections, autoimmunity, allergies, and neoplasias. Usually, its onset occurs in childhood or during the second and third decades of life; however, the diagnosis is made, on average, 6 to 7 years afterwards. As a consequence, antibody defects can lead to sequelae. Here we describe the clinical-laboratory characteristics, treatment, and prognoses of patients with hypogammaglobulinemia. An observational, cross-sectional, and retrospective study of patients attending the recently established outpatient group of Clinical Immunology between 2013 and 2018 was carried out. Patients with IgG levels below 2 standard deviations from the mean values for the age and/or impaired antibody response were included. Eight patients (3 F and 5 M; median age=41 years (16–65), average symptom onset at 25 years (1–59), and time to diagnosis of 10 years were included. The main infections were: sinusitis in 7/8, pneumonia in 6/8, otitis in 2/8, tonsillitis and diarrhea in 2/8, and diarrhea in 2/8 patients. Hypothyroidism was identified in 4/8 (50%) patients. Rhinitis was found in 7/8 (87.5%) and asthma in 3/8 (37.5%) patients. The tomographic findings were consolidations, atelectasis, emphysema, ground glass opacity, budding tree, bronchial thickening, and bronchiectasis. Immunoglobulin reposition was used between 466 and 600 mg/kg monthly (514.3 mg·kg-1·dose-1). Prophylactic antibiotic therapy was included in 7/8 (87.5%) patients. Airway manifestations prevailed in patients with hypogammaglobulinemia. There is a need for educational work to reduce the time of diagnosis and initiation of treatment, avoiding sequelae.

International consensus statement on allergy and rhinology: rhinosinusitis 2021

“…In the subset of adult patients who have CRS that is refractory to usual therapy, primary immunodeficiency (PID) should be considered. The most common clinical manifestations of PID include RS, chronic otitis media, and chronic lung diseases (CLDs) such as pneumonia and bronchiectasis 926–932 . An association between hypoimmunoglobulinemia and CRS has been described in the literature and multiple studies have demonstrated PID as a risk factor for the development of CRS 492,493,929,930,933–940 .…”

“…The most common clinical manifestations of PID include RS, chronic otitis media, and chronic lung diseases (CLDs) such as pneumonia and bronchiectasis 926–932 . An association between hypoimmunoglobulinemia and CRS has been described in the literature and multiple studies have demonstrated PID as a risk factor for the development of CRS 492,493,929,930,933–940 . The association is further strengthened in that other studies show an increased incidence and prevalence of RS in patients with immune dysfunction 493,926,927,941 …”

“…CVID, specific antibody deficiency (SAD), X‐linked hypogammaglobulinemia, and several other disorders of humoral immunity are frequently referenced as contributing factors to chronic or recurrent recalcitrant RS 40,928,931,932,939,942–944 . A number of selective Ig deficiencies, specifically those involving IgG3 subclass, IgA, and IgM, have been consistently identified in this group of patients 492,493,804,927,929,930,933,936,938–942,945–949 . Pre‐immunization antipneumococcal titers have shown to be decreased as well, particularly in patients with the more severe forms of immunodeficiency such as CVID; patients with refractory RS can also demonstrate poor functional antibody responses to immunization 492,493,941,943 .…”

“…Yet there are no consensus guidelines on the use of antibiotics in refractory CRS with immunodeficiency. Pimenta et al report a cross‐sectional study of 8 patients with hypogammaglobulinemia in which most received prophylactic antibiotic therapy, however, no therapeutic outcomes were discussed 930 . Prophylactic antibiotics may reduce infections in immunodeficient patients, but, there is an increased concern on antimicrobial resistance and alterations to the sinus microbiome.…”

Pediatric Prediction Model for Low Immunoglobulin G Level Based on Serum Globulin and Illness Status

“…In general, IgGLo is defined as a decrease in IgG concentrations at least 2 standard deviations (SDs) compared to mean age-specific IgG level. However, the risk of recurrent and severe infections generally occurs particularly when serum IgG levels are <500 mg/dl ( 13 ). Therefore, in our study, IgGLo was defined as a serum IgG level <500 mg/dl, regardless of age.…”