Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Over 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES]. METHODS: Patients receiving IBD care at a single centre were prospectively enrolled in a longitudinal data repository starting in 2012. WES was offered with enrollment. Enrolled patients were filtered by age of diagnosis <6 years to comprise a VEOIBD cohort. Monogenic disease was identified by filtering proband variants for rare, loss-of-function, or missense variants in known VEOIBD genes inherited according to standard Mendelian inheritance patterns. RESULTS: This analysis included 216 VEOIBD patients, followed for a median of 5.8 years. Seventeen patients [7.9%] had monogenic disease. Patients with monogenic IBD were younger at diagnosis and were more likely to have Crohn's disease phenotype with higher rates of stricturing and penetrating disease and extraintestinal manifestations. Patients with monogenic disease were also more likely to experience outcomes of intensive care unit [ICU] hospitalisation, gastrostomy tube, total parenteral nutrition use, stunting at 3-year follow-up, haematopoietic stem cell transplant, and death. A total of 41 patients [19.0%] had infantile-onset disease. After controlling for monogenic disease, patients with infantile-onset IBD did not have increased risk for most severity outcomes. CONCLUSIONS: Monogenic disease is an important driver of disease severity in VEOIBD. WES is a valuable tool in prognostication and management of VEOIBD.

Strongyloidiasis in Ontario: Performance of diagnostic tests over a 14-month period.

BACKGROUND: We evaluated the performance of stool microscopy, serology, and real time PCR (qPCR) for the diagnosis of strongyloidiasis at our reference laboratory. METHODS: Using a convenience sample of specimens submitted between April 1, 2014 and May 31, 2015, positivity rates and performance characteristics were calculated. RESULTS: During the enrolment period, 17,933 stool specimens were examined for O&P, 14 of which were positive for Strongyloides larvae. For stool specimens serially positive for larvae, mean duration of larval shedding was 12.7 days following the initial positive specimen, while for sputum and urine, it was 12 and 2 days, respectively. During the enrolment period, 3258 specimens were processed for Strongyloides serology, 200 of which were reactive (6.1%), 210 indeterminate (6.5%), and 2848 non-reactive (87.4%). qPCR was positive in 11 of 12 (91.7%) stool specimens containing larvae, and negative in all stool specimens without larvae by microscopy. There was no cross-reactivity of Strongyloides-specific qPCR to other stool protozoa or helminths. CONCLUSIONS: In the absence of immunosuppression, larval burden in strongyloidiasis is low, limiting the utility of microscopy, and favoring serologic testing. However, false negative serology can occur in those with hyperinfection necessitating a combined diagnostic approach. qPCR was insufficiently sensitive to replace microscopy for detection of larvae.