CVID-associated intestinal disorders in the USIDNET registry: An analysis of disease phenotypes, functional status, comorbidities, and treatment

Abstract

Non-infectious intestinal disorders occur in a substantial proportion of patients with common variable immunodeficiency (CVID). These generally do not improve with immunoglobulin replacement and are linked to higher mortality. Here we report the phenotypic distribution of intestinal disorders, comorbidities, and treatment strategies in a large cohort of patients with CVID. The United States Immunodeficiency Network database included 1415 patients with CVID, of which 290 had intestinal disorders. We compared the prevalence of comorbidities, malignancies, and functional status between patients with and without intestinal disorders, and describe agents used to treat them. Intestinal disorders were present in 20% of patients, with chronic diarrhea (40%) and colitis (21%) being the most common diagnoses. Patients with intestinal disorders were more likely to require enteral or parenteral nutrition (p<0.01) and had lower Karnofsky-Lansky scores (p<0.01) compared to those without. Autoimmune gastritis/pernicious anemia (p<0.01), vitamin D deficiency (p<0.01), hepatic disease (p<0.01), interstitial lung disease (p<0.01), granulomatous disease (p<0.01), lymphoma (p=0.01), autoimmune hematologic disorders (p<0.01) including immune thrombocytopenic purpura (p=0.04), and mutations in CTLA4 (p=0.04) were more prevalent in the intestinal disease cohort. Corticosteroids, followed by azathioprine, rituximab, infliximab, and mesalamine were the most commonly reported pharmacotherapies for intestinal disorders. Patients with CVID who have intestinal disorders are more likely to have other autoimmune/inflammatory comorbidities and lymphoma. This combination of sequelae may explain the lower functional status observed here and the higher mortality reported previously. Corticosteroids were the most commonly employed treatment, yet the optimal therapeutic strategy is unclear.