Morbidity and mortality in common variable immune deficiency over 4 decades

Abstract

The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P ‫؍‬ .004). Ninetyfour percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organspecific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P ‫؍‬ .009) and were more likely to develop lymphoma (P ‫؍‬ .04); 19.6% of patients died, a significantly shorter survival than age-and sexmatched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio ‫؍‬ 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy. (Blood. 2012;119(7):1650-1657)

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

“…The most common autoimmune manifestation is cytopenia: autoimmune thrombocytopenia (ITP) is found in up to 14% of patients followed by autoimmune hemolytic anemia (AHA), which is found in up to 7% (8). Sometimes ITP and AHA coexist in Evans Syndrome.…”

“…Other autoimmune manifestations of CVID include idiopathic neutropenia, vitiligo, pernicious anemia, anti-phospholipid syndrome, presence of anti-IgA antibodies, rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, Sjogren s syndrome, psoriasis, thyroiditis, uveitis, and vasculitis (5,8,10).…”

“…Lung involvement is the main cause of death in CVID patients (8), and its prevalence increases up to 46.4% during followup (10). Chronic lung disease (CLD) is partly caused by recurrent, unchecked infections that result in the development of bronchiectasis in a percentage of patients that varies from 4 to 76%, depending on the cohort (5).…”

“…Chronic lung disease (CLD) is partly caused by recurrent, unchecked infections that result in the development of bronchiectasis in a percentage of patients that varies from 4 to 76%, depending on the cohort (5). However, at least half of the patients develop CLD in the absence of bronchiectasis (8). These patients commonly show polyclonal lymphoid infiltration of the lung, and biopsies can reveal features of reactive lymphoid hyperplasia or granulomatous inflammation (13).…”

“…of subjects with systemic granulomatous disease (8). It is however noteworthy that this prevalence may be underestimated because many patient do not undergo lung biopsy.…”