Noninfectious complications of common variable immunodeficiency increase mortality risk

LOUISVILLE, Ky. — Patients with noninfectious complications of common variable immunodeficiency, such as gastrointestinal disease, malignancy and rheumatoid arthritis, had increased mortality risk, according to study results.

Men with common variable immunodeficiency (CVID) also appeared to be at greater risk for vitamin D deficiency and faced a greater risk for mortality of hematologic malignancy than women, according to the results, which were presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

“Common variable immunodeficiencies encompass a variety of clinical phenotypes, and there are multiple ways that immune dysregulation of CVID can manifest, with the two main buckets being recurrent infections and noninfectious manifestations, or these autoimmune and autoinflammatory complications,” Michael D'Netto, MD, allergy and immunology fellow at Mayo Clinic in Rochester, Minnesota, said during his presentation. “We know that many of these noninfectious complications have been identified, and prior studies have shown that some of these are associated with an increased risk for morality.”

D’Netto and colleagues sought to further evaluate how noninfectious complications affect mortality among patients with CVID at their institution.

Determining the mortality risk of noninfectious complications served as the study’s primary endpoint, and creating a survival model served as the secondary endpoint.

D’Netto and colleagues conducted a retrospective chart review of 138 patients (56.5% women; mean age at diagnosis, 45.2 years; 94.1% white) with CVID, evaluating their demographics, baseline laboratory values, nutritional status, recent hospitalizations, mortality and prevalence of noninfectious complications.

Overall, 113 (82%) patients had at least one noninfectious complication, which most commonly affected the pulmonary (n = 73) and hematologic (n = 48) organ systems, with some patients having more than one noninfectious complication. Other complications including gastrointestinal disease (n = 35); rheumatologic disease (n = 18), including four patients with an unspecified rheumatologic condition; and nonhematologic malignancy (n = 20).

“This 82% of patients with a noninfectious complication is a bit higher than a variety of publications, maybe related to the complexity of patients who are seen at our institution,” D’Netto said.

The researchers also found that, overall, men were more likely than women to have vitamin D deficiency (27.7 ng/mL vs. 41.3 ng/mL; P = .014).

Using Cox regression univariate analysis, results showed that patients appeared at increased risk for mortality if they had gastrointestinal disease (HR = 3.47; 95% CI, 1.06-11.38), large intestine pathology (HR = 4.34; 95% CI, 1.13-16.73), norovirus enteropathy (HR = 8.25; 95% CI, 1.77-38.52), autoimmune enteropathy (HR = 4.74; 95% CI, 1-22.43), nodular regenerative hyperplasia (HR = 7.06; 95% CI, 1.47-33.94), hematologic malignancy (HR = 7.95; 95% CI, 2.51-25.2), non-hematologic malignancy (HR = 7.69; 95% CI, 2.22-26.65) and rheumatoid arthritis (HR = 7.89; 95% CI, 1.65-37.75).

When researchers stratified results by sex, they found that only hematologic malignancy reached statistical significance, with a smaller risk for women (HR = 0.05; 95% CI, 0-0.38) and men at significantly greater risk. A similar trend was seen for nonhematologic malignancy (HR = 0.28; 95% CI, 0.08-1.06).

In their survival curve, researchers observed the greatest risk for death within the first 10 years of diagnosis, with no difference between men and women, which may have been due to the small population size, D’Netto said.

“Our findings may warrant closer surveillance for noninfectious complications and nutritional assessments in patients with CVID,” he added.