Pediatric Collagenous Gastritis: Clinical and Histologic Outcomes in a Large Pediatric Cohort.

OBJECTIVE: The aim of the study was to present the clinical characteristics, treatment, and outcomes of pediatric collagenous gastritis (CG). METHOD: This is a retrospective cohort study. Patients were identified via query of the institutional pathology database. Clinical data was obtained by review of medical records. RESULTS: Forty patients (57.5% female) were identified, mean age 11.3 ±â€Š3.7 years (2-16years). Isolated CG was present in 66.7%, coexisting collagenous duodenitis (CD) in 17.5%, collagenous colitis (CC) in 7.5%, and collagenous ileitis in 2.5%. Atopic comorbidities were found in 25%, autoimmune comorbidities in 12.5%. PRESENTING SYMPTOMS: Abdominal pain (77.5%), vomiting (65%), anemia (57.5%), nausea (55.5%), diarrhea (32.5%), anorexia (25.0%), weight loss (25%), gastrointestinal bleed (22.5%), poor growth (20%), poor weight gain (12.5%). ENDOSCOPIC FINDINGS: All had abnormal endoscopic findings on esophago-gastro-duodenoscopy (EGD), most commonly gastric nodularity (77.5%), visible blood (20%), erosions/superficial ulcerations (10%), ulcers (7.5%). Histologically, all patients had increased subepithelial collagen deposition. TREATMENT: A variety of medications aimed towards inflammation and symptomatic treatment were used. Patients with anemia received iron supplementation and responded. Otherwise, there was no significant association of clinical or histologic improvement with specific treatments. CLINICAL AND HISTOLOGIC OUTCOMES: 87.5% reported improvement or resolution of symptoms at the last follow-up (34.8 ±â€Š27.0 months). Persistent sub-epithelial collagen was noted in 73.1% on the last EGD. CONCLUSIONS: Despite persistent findings of increased sub-epithelial collagen deposition during the follow-up period, most patients with CG show remission or resolution of clinical symptoms. Anemia responds to iron supplementation in all patients.

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.

Where Did the Blood Go?: A Meckel's Diverticulum Bleed Without Hematochezia or Melena.

A 2-year-old patient with chronic abdominal pain presented with acutely worsening abdominal pain and acute anemia. The patient had no stigmata of bleeding including no hematemesis, melena or hematochezia, but had falling hemoglobin and hematocrit over the course of 24 hours. Abdominal ultrasound and computerized tomography showed a large cystic, fluid filled mass in the right midabdomen. The patient was taken to the operating room and a blood-filled mass arising from the ileum was identified and resected by the surgical team. Pathology was consistent with Meckel's diverticulum with heterotopic gastric mucosa. This is an atypical presentation of Meckel's diverticulum with bleeding contained within the diverticulum rather than bleeding in the intestinal lumen. Gastroenterologists must consider this unusual presentation when encountering progressive, acute anemia even in the absence of overt gastrointestinal blood loss.

Pediatric Collagenous Gastroenterocolitis Successfully Treated with Methotrexate.

A two-and-one-half-year-old previously healthy female presented with a ten-week history of watery diarrhea, nonbilious and nonbloody emesis, and low-grade fevers. She was found to have severe hypoalbuminemia and hypogammaglobulinemia. Her symptoms persisted, and she became dependent on parenteral nutrition. Biopsies obtained during subsequent endoscopic and colonoscopic studies revealed findings consistent with collagenous gastroenterocolitis. She responded to an empiric course of prednisone, but her symptoms recurred shortly after transitioning to oral budesonide. After successful reinduction with intravenous prednisone, intramuscular methotrexate was initiated. She remained asymptomatic during a 15-month course of therapy, and she continued to do well clinically until approximately nine months after weaning off methotrexate. At that point, she experienced a recurrence of diarrhea, and repeat endoscopic evaluation confirmed collagenous colitis. This responded nicely to a short course of oral budesonide, and she has since remained asymptomatic and off any therapy.

Fatal Central Nervous System Disease Following First Infliximab Infusion in a Child With Inflammatory Bowel Disease.

BACKGROUND: Infliximab is used in the treatment of inflammatory bowel disease. Previously reported neurological complications include central and peripheral demyelinating disorders and neuropathies occurring months into therapy. PATIENT DESCRIPTION: A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded. Neurological examination revealed minimally reactive pupils and otherwise absent brainstem reflexes. Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage. Magnetic resonance imaging showed diffusion restriction concerning for ischemia with areas of ring enhancement suggestive of inflammation. Vessel imaging was normal, and cerebrospinal fluid and serum studies showed only an extremely elevated level of d-dimer. Echocardiogram showed depressed ventricular function but neither intracardiac shunt nor thrombus. Within four days he met criteria for brain death. Autopsy was refused. CONCLUSIONS: This is the first report of a fulminant, fatal central nervous system process to occur after an initial dose of infliximab. The differential diagnosis includes multifocal arterial strokes and a devastating demyelinating process.

Thrombosis and inflammatory bowel disease: a call for improved awareness and prevention.

Thrombotic complications in patients with inflammatory bowel disease (IBD) are common and require improved awareness and prevention. In this review the interface between IBD and thrombosis is discussed, with emphasis on risk assessment and data to aid clinical decision making. Thromboembolic complications are 3-fold more likely in IBD patients than controls and the relative risk exceeds 15 during disease flares. Improved assessment of thrombosis risk for an individual patient includes thorough personal and family history and awareness of prothrombotic medications and lifestyle choices. Patients with the highest risk of thrombosis are those with active colonic disease, personal or strong family history of thrombosis, and those with significant acquired risk factors. Combined risk factors or hospitalization should prompt mechanical thromboprophylaxis. Indications for prophylactic anticoagulation are not defined currently by clinical studies, especially in pediatric patients, although some groups now advocate prophylactic anticoagulation for all hospitalized IBD patients and even some outpatients with disease flares. Thrombosis management requires a multidisciplinary therapeutic approach to balance anticoagulation and bleeding risk. While bleeding may occur with anticoagulation in IBD, data and experience indicate that therapeutic heparin is safe and bleeding manifestations can be managed supportively in most patients. Until prospective trials of prophylactic anticoagulation are published, management of thrombotic risk and prophylaxis in IBD will remain a clinical challenge.

Regulatory regions in the rat lactase-phlorizin hydrolase gene that control cell-specific expression.

OBJECTIVES: Lactase-phlorizin hydrolase (LPH) is an enterocyte-specific gene whose expression has been well-characterized, not only developmentally but also along the crypt-villus axis and along the length of the small bowel. Previous studies from the authors' laboratory have demonstrated that 2 kb of the 5'-flanking region of the rat LPH gene control the correct tissue, cell, and crypt-villus expression in transgenic animals. METHODS: To examine further the regulation conferred by this region, protein-DNA interactions were studied using DNase I footprint analyses in LPH-expressing and nonexpressing cell lines. Functional delineation of this 5'-flanking sequence was performed using deletion analysis in transient transfection assays. RESULTS: Studies revealed a generally positive activity between -74 and -37 bp, a cell-specific negative region between -210 and -95 bp, and additional elements further toward the 5'-terminus that conferred a highly cell-specific response in reporter activity. Computer analysis of distal regions encompassing identified footprints revealed potential binding sites for various intestinal transcription factors. Co-transfection and electromobility shift assay experiments indicated binding of HNF3beta at three sites relevant to LPH expression. CONCLUSIONS: The data demonstrate that the cell specificity of LPH gene expression depends upon both positive and negative interactions among elements in the first 2 kb of the LPH 5'-flanking region.