Linking Genetic Diagnosis to Therapeutic Approach in Very Early Onset Inflammatory Bowel Disease: Pharmacologic Considerations.

Very early onset inflammatory bowel disease (VEO-IBD) is diagnosed in children < 6 years of age, and in rare cases may be due to an identifiable monogenic cause. Recent advances in genetic testing have allowed for more accurate diagnosis, with as many as 100 genes now known to be associated with monogenic inflammatory bowel disease. These genes are involved in many immune pathways and thus may represent potential avenues for targeted precision medicine with pharmacologic treatments aimed at these. This review describes the broad classifications of monogenic disorders known to cause VEO-IBD, as well as empiric and disease-specific medical therapies. These include immune-modulating or immunosuppressant medications, nutritional therapy, surgery, and hematopoietic stem cell transplantation. We aim to provide an overview of the current state of targeted therapy for VEO-IBD.

Risk factors, morbidity, and treatment of thrombosis in children and young adults with active inflammatory bowel disease.

OBJECTIVES: Pediatric inpatients with inflammatory bowel disease (IBD) are rarely considered for thromboprophylaxis because of concerns about safety and underappreciation of thrombotic risk. We characterized thromboembolism (TE) in children and young adults with inflammatory bowel disease (IBD) at a single tertiary care hospital. METHODS: We performed a retrospective review of an inpatient billing database for all IBD admissions with colonic involvement and an anticoagulation database for thrombotic complications from 2006 to 2011. RESULTS: Of 532 patients admitted with IBD with colonic involvement, 10 (1.9%) had TE (9 venous, 1 arterial), 2 of whom had recurrent thrombosis. Many of the events resulted in considerable morbidity, including 4 cerebrovascular events and 2 pulmonary emboli. Established risk factors in IBD colitis inpatients with TE included: indwelling catheter (4/10), first-degree family member with TE (2/10), hereditary thrombophilia (3/10), smoking (1/10), oral contraceptive (1/5 females), and thalidomide (1/10). Additionally, most (8/10) patients had acquired thrombophilia, mostly elevation of factor VIII and anticardiolipin antibodies. Patients with IBD and TE received therapeutic anticoagulation without significantly increased bleeding. Thrombus resolution was documented in 7 cases, persistence in 2 cases and recurrence in 2 cases. CONCLUSIONS: Pediatric inpatients hospitalized with IBD with colonic involvement have increased risk of TE, including complications of pulmonary embolism, recurrence, persistence, and indefinite long-term anticoagulation. Therapeutic anticoagulation in patients with IBD with active colitis appears safe. We identified both inherited thrombophilias and acquired risk factors in patients with IBD and TE. We presently use risk stratification and recommend prophylactic anticoagulation in high-risk patients.