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OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.

OBJECTIVES: To systematically review the current evidence on Helicobacter pylori-negative chronic gastritis including natural history, available therapies and outcomes. METHODS: Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori-negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included. RESULTS: A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross-sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%-45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses. CONCLUSIONS: Helicobacter pylori-negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult-paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.