SUMMARY BackgroundStudies have found that depression is more frequent in patients with inflammatory bowel disease (IBD) than the general population. Clinicians are now trying to pinpoint risk factors for psychological impairment in the IBD population.

Human polyomavirus 7 (HPyV7) is one of 11 HPyVs recently discovered through genomic sequencing technologies. Two lung transplant recipients receiving immunosuppressive therapy developed pruritic, brown plaques on the trunk and extremities showing a distinctive epidermal hyperplasia with virus-laden keratinocytes containing densely packed 36-45-nm icosahedral capsids. Rolling circle amplification and gradient centrifugation testing were positive for encapsidated HPyV7 DNA in skin and peripheral blood specimens from both patients, and HPyV7 early and capsid proteins were abundantly expressed in affected tissues. We describe for the first time that HPyV7 is associated with novel pathogenicity in some immunosuppressed individuals.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exomesequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10 −10 ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10 −10 ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Background Given the rising prevalence of diabetes mellitus (DM) and the limited data on its effect on the course of inflammatory bowel disease (IBD), we characterized multiyear patterns of disease severity in a cohort of IBD patients with coexistent DM. Methods Data of consented IBD patients followed prospectively in a natural history registry at a tertiary center between 2009 and 2017 were analyzed. Patients with ≥3 years of clinical follow-up were included. Patients identified with a diagnosis of DM were compared with 400 consecutive IBD controls without a diagnosis of DM, no laboratory evidence of hyperglycemia, and no history of antihyperglycemic treatment. Results Out of 2810 IBD patients, 141 (5%) had DM (IBD DM; 44% ulcerative colitis, 56% Crohn’s disease, 48.2% female). IBD DM had higher use of 5-aminosalicylic acid (5ASA) agents (P = 0.04), narcotics (P &lt; 0.001), and antibiotics (P = 0.007) but not immunomodulators and/or biologics compared with IBD controls. When analyzing biomarkers of severity, IBD DM demonstrated higher frequencies of elevated C-reactive protein (CRP; P = 0.006), elevated erythrocyte sedimentation rate (ESR; P = 0.001), eosinophilia (P = 0.004), monocytosis (P = 0.02), and hypoalbuminemia (P = 0.001). IBD DM had worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P &lt; 0.001). IBD DM had increased health care utilization compared with controls (emergency room usage P = 0.008, hospitalizations P &lt; 0.001, gastroenterology clinic visits P &lt; 0.001, and median annual charges P &lt; 0.001). Among IBD DM patients, the use of immunomodulators and/or biologics was not associated with further complications as measured by antibiotic use or hospitalizations. Conclusions This study of a large IBD cohort suggests that DM in IBD may be associated with increased disease severity and that there may be room for increasing use of highly effective immunomodulator and/or biologic agents in this group.

Background Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization. Methods We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type. Results A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P &lt; 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P &lt; 0.001) and an increased likelihood of hospitalization (adjusted odds ratio [AOR], 4.5; P &lt; 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P &lt; 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P &lt; 0.05). Conclusions Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.