Extra-Immunologic Manifestations of Common Variable Immunodeficiency in Pediatric Versus Adult Patients

Rationale: Common variable immunodeficiency (CVID) is a primary immunodeficiency defined by hypogammaglobulinemia, poor antibody response to vaccinations, and frequent or chronic bacterial infections.  CVID has also been associated with autoimmunity, increased risk of lymphoid malignancy, enteropathy/colitis, and granulomatous disease. We sought to define other extra-immunologic manifestations in pediatric and adult patients with CVID.

Methods: We utilized retrospective data made available from the United States Immunodeficiency Network (USIDNET). 231 pediatric patients (i.e. ≤17 years old) and 339 adult patients (i.e. ≥18 years old) were identified in USIDNET with a diagnosis of CVID, and had at least one documented clinical condition. Chi-squared testing was used to compare conditions between pediatric and adult patients.

Results: Frequently reported extraimmunologic manifestations in both pediatric and adult CVID patients included non-infectious diarrhea (22.51% vs 28.61%, respectively), fatigue (30.74% vs 38.64%), gastroesophageal reflux disease (17.75% vs 23.01%) and headaches (8.23% vs 14.75%). Frequently reported conditions with clinically significant (p <0.05) enrichment in adult CVID patients included aches/chronic pain (9.52% vs 23.60%, p<0.001), arthralgia (10.82% vs 17.99%, p=0.019), anxiety (1.73% vs 5.31%, p=0.029), depression (6.49% vs 22.42%, p<0.001), hypothyroidism (3.03% vs 10.91%, p=0.001), non-lymphoid malignancy (2.60% vs 11.50%, p<0.001) and osteopenia (2.60% vs 7.96%, p=0.007).  

Conclusions: Chronic pain (“aches” and arthralgia), anxiety, and depression are underappreciated but frequently reported co-morbid conditions in CVID. Regular screening for depression and anxiety in adult CVID patients may be justified. Further research may be warranted to understand how best to provide psychosocial supports to both pediatric and adult patients with CVID.