Histologic findings at diagnosis as predictive markers of clinical outcome in pediatric ulcerative colitis.

BACKGROUND: The role of histological inflammation at diagnosis as a possible prognostic factor for disease course has not been investigated. AIMS: To assess whether histologic findings at diagnosis could predict clinical outcomes and evaluate the association between clinical, biochemical, endoscopic, and histological findings. METHODS: Prospective single-center study including pediatric UC patients with a minimum follow-up of 12 months. The association between histological activity (Nancy Index, Robarts Histopathology Index, and Geboes Score) and 12-month clinical outcomes was evaluated. Secondarily, we assessed the correlation between histological scores and endoscopic and inflammatory markers at the diagnosis. Inter-observer agreement for histologic and endoscopic scores was also evaluated. RESULTS: Forty-nine UC patients were included. No association was found between 1-year clinical relapse and the three histological indices at diagnosis (p > 0.05). Good concordance was found among the three histological scores (p < 0.001), and between all histological and endoscopic indices (p < 0.05). No correlation was found between histologic scores and serum inflammatory markers. Inter-observer agreement was good for eMayo, Nancy and Robarts score (k = 0.71, k = 0.74 and k = 0.68, respectively) and moderate for Geboes (k = 0.46). CONCLUSIONS: Histological findings at diagnosis cannot be used as a predictor of the disease course. The three histological scores used in routine clinical practice show an overall good correlation and reliability.

The use of urine peptidomics to define dietary gluten peptides from patients with celiac disease and the clinical relevance.

INTRODUCTION: Determination of urinary gluten immunogenic peptides (GIP) has emerged as one of the most attractive test to monitor the adherence to the gluten-free diet (GFD) of patients with celiac disease (CD), being a simple, noninvasive and direct method to detect gluten contamination of the GFD. AREAS COVERED: We conducted a scoping review in Medline (PubMed) of articles published up to April 2023 that analyzed any aspect of the clinical relevance of the use of urinary GIP measurement in patients with CD. A total of 17 articles reporting the clinical use of urinary peptidomics for the follow-up of CD patients were finally included. EXPERT OPINION: Available data suggest that a negative urinary GIP result is a reliable noninvasive predictor of intestinal mucosa healing in CD patients treated with the GFD, especially if testing three urine samples on different days including the weekend. Due to conflicting results about the sensitivity and the specificity of the urinary GIP determination, additional in-depth information is needed, particularly related to (1) the relationship between the amount of ingested gluten and the quantity of urinary GIP excreted in treated CD patients, (2) the GIP kinetics and best timing for sample collection.

Outcome of Very Early Onset Inflammatory Bowel Disease Associated With Primary Sclerosing Cholangitis: A Multicenter Study From the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND: Whether primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed before 6 years (ie, VEO-IBD) has a distinct phenotype and disease course is uninvestigated. We aimed to analyze the characteristics and natural history of VEO-PSC-IBD, compared with early and adolescent-onset PSC-IBD. METHODS: This is a multicenter, retrospective, case-control study from 15 centers affiliated with the Porto and Interest IBD group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every 6 months. Inflammatory bowel disease-related (clinical remission, need for systemic steroids and biologics, and surgery) and PSC-related (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, or death) outcomes were compared between the 2 groups. RESULTS: Sixty-nine children were included, with a median follow-up of 3.63 years (interquartile range, 1-11): 28 with VEO-PSC-IBD (23 UC [82%], 2 IBD-U [7%] and 3 [11%] CD), and 41 with PSC-IBD (37 UC [90%], 3 IBDU [7.5%] and 1 [2.5%] CD). Most patients with UC presented with pancolitis (92% in VEO-PSC-UC vs 85% in PSC-UC, P = .2). A higher number of patients with VEO-PSC-IBD were diagnosed with PSC/autoimmune hepatitis overlap syndrome than older children (24 [92%] vs 27 [67.5%] PSC-IBD, P = .03), whereas no other differences were found for PSC-related variables. Time to biliary strictures and infective cholangitis was lower in the VEO-PSC-IBD group (P = .01 and P = .04, respectively), while no difference was found for other outcomes. No cases of cholangiocarcinoma were reported. CONCLUSIONS: Primary sclerosing cholangitis related to inflammatory bowel disease has similar baseline characteristics whether diagnosed as VEO-IBD or thereafter. A milder disease course in terms of biliary complications characterizes VEO-PSC-IBD.

Very early onset primary sclerosing cholangitis associated with IBD (VEO-PSC-IBD) often presents with autoimmune features and shows a milder PSC disease course than later-onset disease. These findings highlight the significance of studying the distinctive genetic and pathophysiological factors specific to VEO disease.

Nonceliac gluten sensitivity.

PURPOSE OF REVIEW: To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel syndrome (IBS)-like manifestations. RECENT FINDINGS: The recent description of disease-triggering wheat components other than gluten, such as fructans and amylase-trypsin inhibitors (ATIs), definitely suggests that nonceliac wheat sensitivity (NCWS) is a better 'umbrella' terminology than NCGS. Self-reported NCWS is very common worldwide, particularly in patients seen at the gastroenterology clinic, but many of these diagnoses are not confirmed by standard clinical criteria. A biomarker of NCWS is still lacking, however, subtle histological features at the small intestinal biopsy may facilitate diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD). The GFD has proven to be an effective treatment of a significant proportion of NCWS-related IBS patients. Dietary therapies for IBS, including the GFD, should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Pioneer studies are under way to test the therapeutic efficacy of supplemental gluten-digesting enzyme preparations in patients with NCWS. SUMMARY: Recent studies highlight interesting pathophysiological and clinical features of NCWS. Many questions remain, however, unanswered, such as the epidemiology, a biomarker(s), and the natural history of this clinical entity.

Induction of Remission With Exclusive Enteral Nutrition in Children With Crohn's Disease: Determinants of Higher Adherence and Response.

BACKGROUND: Exclusive enteral nutrition (EEN) is the first choice to induce remission and promote mucosal healing in pediatric Crohn's disease (CD). However, full adherence to EEN treatment may be problematic for children with CD. METHODS: The goal of the current multicenter retrospective study was to define predictive factors of nonadherence to treatment and nonremission at the end of induction treatment. Those data together were analyzed with the ultimate goal of trying to define an individualized induction treatment for children with CD. RESULTS: Three hundred seventy-six children with CD from 14 IBD pediatric referral centers were enrolled in the study. The rate of EEN adherence was 89%. Colonic involvement and fecal calprotectin >600 µg/g at diagnosis were found to be associated with a reduced EEN adherence. Exclusive enteral nutrition administered for 8 weeks was effective for inducing clinical remission in 67% of the total cohort. Factors determining lower remission rates were age >15 years and Pediatric Crohn's Disease Activity Index >50. CONCLUSION: Although EEN is extremely effective in promoting disease remission, several patients' related factors may adversely impact EEN adherence and response. Personalized treatments should be proposed that weigh benefits and risks based on the patient's disease location, phenotype, and disease activity and aim to promote a rapid control of inflammation to reduce long-term bowel damage.

The Clinical Spectrum of Inflammatory Bowel Disease Associated With Specific Genetic Syndromes: Two Novel Pediatric Cases and a Systematic Review.

Background and Aims: Inflammatory bowel disease (IBD) is a typical polygenic disorder and less frequently shows a monogenic origin. Furthermore, IBD can originate in the context of specific genetic syndromes associated with a risk of autoimmune disorders. We aimed to systematically evaluate the prevalence of IBD in specific genetic syndromes and to review the clinical characteristics of the published cases. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies describing patients with IBD and a genetic syndrome and/or studies indicating the prevalence or incidence of IBD in subjects with a genetic syndrome were included. Results: Forty-six studies describing a total of 67 cases of IBD in six genetic syndromes and two personally assessed unpublished cases were included in the review. The majority of cases were associated with Turner syndrome (TS) (38 cases), Down syndrome (DS) (18 cases) and neurofibromatosis type 1 (NF1) (8 cases). Sporadic cases were described in DiGeorge syndrome (2), Kabuki syndrome (2), and Williams syndrome (1). The prevalence of IBD ranged from 0.67 to 4% in TS and from 0.2 to 1.57% in DS. The incidence of IBD was increased in TS and DS compared to the general population. Eight cases of IBD in TS had a severe/lethal course, many of which described before the year 2000. Two IBD cases in DS were particularly severe. Conclusion: Evidence of a greater prevalence of IBD is accumulating in TS, DS, and NF1. Management of IBD in patients with these genetic conditions should consider the presence of comorbidities and possible drug toxicities. Systematic Review Registration: PROSPERO, identifier: CRD42021249820.

Determination of Urinary Gluten Immunogenic Peptides to Assess Adherence to the Gluten-Free Diet: A Randomized, Double-Blind, Controlled Study.

INTRODUCTION: The adherence to a gluten-free diet (GFD) is a trending topic in the management of celiac disease. The aim of our study was to evaluate the diagnostic performance of urinary gluten immunogenic peptides (GIP) determination to detect gluten contamination of the GFD. METHODS: In study A, 25 healthy adults on a standard GFD performed 6 gluten challenges (0, 10, 50, 100, 500, and 1,000 mg) with quantification of urinary GIP before (T0) and during the following 24 hours. In study B, 12 participants on a gluten contamination elimination diet underwent urinary GIP determination at T0 and after challenge with 5 or 10 mg gluten. Urine GIP concentration was determined by an immunochromatographic assay. RESULTS: In study A, 51 of 150 baseline urine samples were GIP+ on GFD and 7 of 17 were GIP+ after the zero-gluten challenge, whereas only 55 of 81 were GIP+ after the 10-1,000 mg gluten challenges. There was no significant change in the 24-hour urinary GIP when increasing gluten from 10 to 1,000 mg. In study B, 24 of 24 baseline urine samples were GIP-, whereas 8 of 24 were GIP+ after 5 or 10 mg of gluten. DISCUSSION: Traces of gluten in the standard GFD may cause positivity of urinary GIP determination, whereas a false negativity is common after a gluten intake of 10-1,000 mg. Owing to the impossibility of standardizing the test in normal conditions, it seems unlikely that urinary GIP determination may represent a reliable tool to assess the compliance to the GFD of patients with celiac disease or other gluten-related disorders.

Is Fecal Calprotectin a Useful Marker for Small Bowel Crohn Disease?

OBJECTIVES: The identification of reliable non-invasive biomarkers of Crohn disease (CD) activity is crucial. Fecal calprotectin (FC) is the most promising one. We aimed to define whether its performance for isolated ileal CD could be as useful as for colonic and ileocolonic disease. METHODS: Retrospective observational study of all pediatric patients affected with CD with FC and inflammatory blood markers performed within one week from an ileocolonoscopy or magnetic resonance enterography. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of FC >50 mcg/g were evaluated for isolated ileal CD (L1), colonic CD (L2) and ilecolonic CD (L3) using ilecolonoscopy and magnetic resonance enterography as the reference standard. The best FC cut-off for each disease location was evaluated using receiver operating characteristic curves. RESULTS: One-hundred seventy-six FC measurements from a total of 98 patients were collected (14.3% L1, 10.2% L2, 75.5% L3). The sensitivity and specificity of FC for L1 CD were 36% and 91%, respectively, compared to 93% and 75% for L2 and 70% and 95% for L3. An FC of 95 mg/kg was identified as the best cut off for identification of active isolated ileal disease, with a sensitivity of 77% and a specificity of 56% [area under the curve (confidence interval [CI] 0.56- 0.97) 0.77, P = 0.02]. CONCLUSIONS: With a sensitivity of 36%, FC alone does not accurately reflect isolated L1 disease activity. A significantly lower threshold should be applied for increasing its performance for isolated small bowel CD monitoring.

Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.

The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); p < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); p = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.

Long-Term Outcome of Potential Celiac Disease in Genetically at-Risk Children: The Prospective CELIPREV Cohort Study.

BACKGROUND: The long-term outcome of potential celiac disease (CD) is still a debated issue. We aimed to evaluate the progression of potential CD versus overt CD after 10-years of follow-up in a cohort of children genetically predisposed to CD. METHODS: The CELIPREV study is prospectively following from birth 553 children with CD-predisposing HLA genes. Children with a diagnosis of potential CD continued to receive a normal diet and repeated the serological screening for CD every year. An intestinal biopsy was taken in presence of persistent positive serology. RESULTS: Overall, 26 (4.7%) children received a diagnosis of potential CD (50% females, median age 24 months). All children were symptom-free. Twenty-three children continued a gluten-containing diet; at 10 years from the first biopsy, three children developed overt CD (13%), 19 (83%) became antibodies negative at 1 year from the first biopsy and remained negative up to 10 years of follow-up and one subject (4%) had fluctuating antibody course with transiently negative values and persistently negative biopsy. CONCLUSIONS: In children genetically predisposed to CD with a diagnosis of potential CD the risk of progression to overt CD while on a gluten-containing diet is very low in the long-term.