ABSTRACT
OBJECTIVES: Patients with inflammatory bowel disease (IBD) tend to self-modify their dietary habits according to disease activity and symptoms. This study aimed to assess the adequacy of the usual diet in Italian children with IBD in comparison to a control group and to the recommended dietary allowances (RDA). METHODS: Dietary habits of IBD children and age- and gender-matched healthy controls were investigated using a validated Food Frequency Questionnaire in five Italian pediatric IBD centers. Adherence to the Mediterranean diet (MD) was assessed using the KID-MED test. Energy (EI), macro, and micronutrients intakes were compared between the two groups, to the RDA and the predicted total energy expenditure (EI/total energy expenditure [TEE]%). RESULTS: IBD subjects (n = 110) reported a lower EI, EI/RDA%, and EI/TEE% compared to controls (n = 110) (p = 0.012, p < 0.0002, and p = 0.014), lower total protein and fat intakes (p = 0.017, p < 0.0001) and lower minerals/RDA, vitamins/RDA and micronutrients/RDA ratio (%). Poor adherence to the MD was more frequent in IBD children compared to controls (p = 0.013). The total EI and carbohydrate intake were inversely correlated with higher disease activity. CONCLUSIONS: Italian children with IBD report an inadequate diet in terms of energy, macro, and micronutrients and have a low adherence to a high-quality MD pattern.
ABSTRACT
Inflammatory bowel diseases (IBD) encompass a group of chronic inflammatory disorders primarily affecting the gastrointestinal tract but capable of impacting various organs, including the eye, with uveitis being the most common ocular condition. We assessed uveitis prevalence and clinical features in a nationwide cohort of pediatric IBD. Among 4229 cases, six patients (four Crohn's disease, one ulcerative colitis, and one unclassified IBD) were identified, resulting in an overall prevalence rate of 141.8 per 100,000 patients. Uveitis onset varied: two before IBD, two after, and two concomitantly. Symptomatic uveitis occurred in 2/6 patients, with anterior involvement in all cases. Median follow-up was 3 years (interquartile range 2-4.75 years). At the last follow-up, 5/6 patients exhibited quiescent IBD, while 4/6 had inactive uveitis. One patient had ocular complications. Uveitis is a rare but potentially complicating manifestation of pediatric IBD.
Subject(s)
Inflammatory Bowel Diseases , Uveitis , Humans , Prevalence , Female , Male , Child , Uveitis/epidemiology , Uveitis/etiology , Adolescent , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Chronic Disease , Child, Preschool , Colitis, Ulcerative/complications , Colitis, Ulcerative/epidemiology , Crohn Disease/complications , Crohn Disease/epidemiology , Follow-Up Studies , Retrospective StudiesABSTRACT
BACKGROUND: The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence. METHODS: We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded. RESULTS: In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; Pâ =â .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; Pâ =â .02). CONCLUSION: In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence.
Data from the IBD SIGENP registry show that the prevalence of major abdominal surgery is 10.8%, with a relatively low occurrence of short-term postoperative complications. The administration of anti-TNF-α drugs after surgery seems to effectively prevent postoperative endoscopic recurrence of disease.
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BACKGROUND: Few drugs have been studied for patients with very early onset inflammatory bowel disease (VEOIBD). This study aimed to evaluate the efficacy and tolerance of thalidomide in children with VEOIBD compared with children with pediatric-onset IBD (pIBD). METHODS: A retrospective cohort study with a control group was conducted. Propensity score 1:1 matching was used to identify control subjects. The treatment persistence; the causes of drug withdrawal; the rate of clinical remission and mucosal healing at 1, 2, and 3 years; and adverse events (AEs) were evaluated in children with VEOIBD treated with thalidomide and compared with children with pIBD. RESULTS: Thirty-nine courses of treatment with thalidomide in VEOIBD and pIBD patients were compared. The treatment persistence at 1, 2, and 3 years was 68.2% (95% confidence interval [CI], 50.8%-80.6%), 57.0% (95% CI, 39.6%-71.1%), and 50.9% (95% CI, 33.7%-65.8%) for VEOIBD patients and 81.7% (95% CI, 65.3%-90.9%), 60.0% (95% CI, 41.7%-74.3%) and 33.0% (95% CI, 17.4%-49.5%) for pIBD patients, respectively (P = .12). A significantly higher proportion of VEOIBD patients discontinued therapy due to lack of efficacy (48.2% vs 17.2%; P = .03), while AEs were the main reason for discontinuation in pIBD patients. Clinical remission and mucosal healing rates did not significantly differ between VEOIBD and pIBD patients. A significatively lower number of VEOIBD patients experienced AEs compared with pIBD patients (14 [35.9%] vs 30 [76.9%]; P = .0005). CONCLUSIONS: Thalidomide is an effective and tolerated treatment in children with VEOIBD. Discontinuation due to lack of efficacy is more frequent, but AEs are less common than in children with pIBD.
Thalidomide is a valid therapeutic option in children with very early onset inflammatory bowel diseases unresponsive to conventional therapies. Discontinuation due to lack of efficacy is more frequent, but adverse events are less common than in children with pediatric-onset inflammatory bowel disease.
Subject(s)
Inflammatory Bowel Diseases , Thalidomide , Child , Humans , Thalidomide/adverse effects , Retrospective Studies , Age of Onset , Drug Tolerance , Inflammatory Bowel Diseases/drug therapyABSTRACT
BACKGROUND: The natural history of ulcerative proctitis (UP) has been poorly investigated in children. AIMS: We aimed to compare the disease course of children with UP at diagnosis to the other locations and to identify extension predictors. METHODS: This was a multicenter, observational study carried out from data prospectively entered in the SIGENP-IBD-Registry. Children with ulcerative colitis (UC) diagnosis and at least 1-year follow-up were included. On the basis of Paris classification UP patients were identified and compared with the other locations. RESULTS: 872 children were enrolled (median age at diagnosis: 11.2 years; M/F: 426/446), of whom 78 (9%) with UP. Kaplan-Meier analysis demonstrated increased cumulative probabilities of disease extension in the E1 group [1 year: 20.3%; 5 years: 52.7%; 10 years: 72.4%] compared to E3 group [1 year: 8.5%; 5 years: 24.9% and 10 years: 60.1%, p=0.001]. No differences were observed comparing E1 and E2 groups [p=0.4]. Cumulative probabilities of surgery at 1, 5 and 10 years were 1.3, 2.8 and 2.8% in the E1 group and 2.5, 8 and 12.8% in the E2-E3-E4 group, respectively (p=0.1). Cox regression analysis demonstrated that PUCAI>35 at diagnosis was associated with endoscopic extension (HR=4.9; CI 95% 1.5-15.2, p=0.006). CONCLUSIONS: UP is associated with similar short and long-term outcomes compared to other locations.
Subject(s)
Colitis, Ulcerative , Proctitis , Child , Humans , Follow-Up Studies , Risk Factors , Disease Progression , Colitis, Ulcerative/diagnosisABSTRACT
BACKGROUND: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD). METHODS: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults. RESULTS: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02). CONCLUSIONS: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.
We aimed to define clusters of disease activity and prognostic factors of disease course in pediatric Crohn's disease. One-third of patients have a quiescent course; however, half of them have an active disease by the end of the 5-year follow-up.
ABSTRACT
Glycogen storage disease type Ib (GSD Ib) is a rare hereditary glycogen disorder that results in inadequate maintenance of glucose homeostasis, accumulation of glycogen in different organs, loss and dysfunction of neutrophils. Crohn's-like disease is observed in up to 24-77% of GDS Ib cases. Recently, empagliflozin has been recommended as a treatment for neutrophil dysfunction in GDS Ib patients with or without Crohn's-like disease. There are no guidelines for the treatment of inflammatory bowel disease (IBD) manifestation in GSD Ib patients, although some cases have been treated with granulocyte colony-stimulating factor and others with IBD conventional therapy, resulting in partial IBD remission. Herein, we describe a child with GDS Ib and Crohn's-like disease who was treated with empagliflozin and achieved complete remission after 2 years of treatment. This case is the first one with such a long follow-up evaluation including endoscopic and magnetic resonance enterography assessment. Our clinical evidence of remission of IBD manifestation in our GSD Ib patient and the role of neutrophils in GDS Ib described in the literature suggest a strong association with IBD pathophysiology and neutrophil function. The use of empagliflozin resulted in significant improvements in gastrointestinal symptoms, reduced drug usage, and enhanced quality of life in the patient, with a favorable safety profile, offering a promising new therapeutic option for this population.
ABSTRACT
Therapeutic drug monitoring (TDM) is a useful tool for optimising the use of anti-TNFα inhibitors in patients with inflammatory bowel diseases (IBDs). Recently, point-of-care methods for the quantification of drug levels and anti-drug antibodies (ADAs) have been developed to overcome the limitations of conventional enzyme-linked immunoabsorbent assays (ELISAs). Here, we evaluated the performance, interchangeability, and agreement between an automated ELISA-based immunoassay (CHORUS Promonitor) and the lateral flow assay (RIDA®QUICK) for the quantification of infliximab (IFX, n = 65) and adalimumab (ADM, n = 58) plasma levels in IBD patients. Thirty-two samples for IFX and twenty-three samples for ADM that tested positively for the presence of ADAs were also used. Overall, data analysis showed a good agreement of ADM trough concentrations (R2 = 0.75) between the two assays as well as for ADA measurement (K > 0.8). However, IFX levels highlighted a weak correlation (R2 = 0.58) between the two kits, with the RIDA®QUICK assay overestimating IFX plasma values by 30% when compared to the CHORUS Promonitor kit. Results from this study show that the two assays are not quantitatively and qualitatively interchangeable due to substantial discrepancies in some results. Accordingly, the same assay should be used for the longitudinal follow-up of IBD patients.
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Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (-308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.
Subject(s)
Crohn Disease , Inflammatory Bowel Diseases , Adult , Humans , Child , Tumor Necrosis Factor-alpha/genetics , Infliximab/therapeutic use , Retrospective Studies , Tumor Necrosis Factor Inhibitors/therapeutic use , Crohn Disease/drug therapy , Crohn Disease/genetics , Pharmacogenetics , Adalimumab/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/geneticsABSTRACT
BACKGROUND: Thiopurine methyltransferase (TPMT) is a crucial enzyme for azathioprine biotransformation and its activity is higher in very early onset inflammatory bowel disease (VEO-IBD) patients than in adolescents with IBD (aIBD). AIMS: The aims of this pharmacoepigenetic study were to evaluate differences in peripheral blood DNA methylation of the TPMT gene and in azathioprine pharmacokinetics in patients with VEO-IBD compared to aIBD. METHODS: The association of age with whole genome DNA methylation profile was evaluated in a pilot group of patients and confirmed by a meta-analysis on 3 cohorts of patients available on the public functional genomics data repository. Effects of candidate CpG sites in the TPMT gene were validated in a larger cohort using pyrosequencing. TPMT activity and azathioprine metabolites (TGN) were measured in patients' erythrocytes by HPLC and associated with patients' age group and TPMT DNA methylation. RESULTS: Whole genome DNA methylation pilot analysis, combined with the meta-analysis revealed cg22736354, located on TPMT downstream neighboring region, as the only statistically significant CpG whose methylation increases with age, resulting lower in VEO-IBD patients compared to aIBD (median 9.6% vs 12%, p = 0.029). Pyrosequencing confirmed lower cg22736354 methylation in VEO-IBD patients (median 4.0% vs 6.0%, p = 4.6 ×10-5). No differences in TPMT promoter methylation were found. Reduced cg22736354 methylation was associated with lower TGN concentrations (rho = 0.31, p = 0.01) in patients with VEO-IBD and aIBD. CONCLUSION: Methylation of cg22736354 in TPMT gene neighborhood is lower in patients with VEO-IBD and is associated with reduced azathioprine inactivation and increased TGN concentrations.
Subject(s)
Azathioprine , Inflammatory Bowel Diseases , Adolescent , Child , Humans , Azathioprine/therapeutic use , DNA Methylation/genetics , Methyltransferases/genetics , Methyltransferases/metabolism , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Immunosuppressive Agents/therapeutic useABSTRACT
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 calprotectinâ >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 ageâ >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.
Subject(s)
Crohn Disease , Humans , Child , Adolescent , Crohn Disease/therapy , Crohn Disease/diagnosis , Enteral Nutrition , Retrospective Studies , Remission InductionABSTRACT
BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. METHODS: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). RESULTS: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. CONCLUSION: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice.
Subject(s)
Child Nutrition Sciences , Gastroenterology , Health Care Surveys , Neurology , Pediatrics , Societies, Medical , Vomiting , Child , Cross-Sectional Studies , Humans , Italy , Practice Guidelines as Topic/standards , Treatment OutcomeABSTRACT
INTRODUCTION: The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009-2018. MATERIALS AND METHODS: Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009-2012, 2013-2015, 2016-2018). RESULTS: The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p =0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). CONCLUSIONS: The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Gastroenterology , Inflammatory Bowel Diseases , Child , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Delayed Diagnosis , Humans , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/epidemiology , Italy/epidemiology , RegistriesABSTRACT
OBJECTIVE: The aim was to assess the awareness and real-life use of biosimilars in inflammatory bowel disease (IBD) among the members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). METHODS: An anonymous web survey involving all SIGENP IBD units which can prescribe biosimilars was conducted between July 1st and December 1st, 2020. The questionnaire included 18 questions addressing the most relevant aspects of biosimilars in pediatric IBD, i.e., advantages, disadvantages, costs, traceability, general knowledge, and real-life use. A descriptive analysis of responses was performed. RESULTS: Responses came from 26 pediatric IBD units in Italy, with representation of the North, the Center, and the South of Italy. The majority of participants (n = 20) had spent > 10 years caring for pediatric IBD patients, and worked in a center which had between 100 and 500 registered pediatric IBD patients (n = 14). Most participants (n = 18) reported they were aware that biosimilars have similar efficacy and safety to those of the originator, and all regarded cost-sparing as the main advantage of biosimilars. Most respondents (n = 20) reported they switch from originator to biosimilar in their everyday clinical practice, mostly during the maintenance phase. Most respondents (n = 20) registered no acute adverse events. Nearly all participants felt totally or very confident in using biosimilars. CONCLUSIONS: A few years after the introduction of the first biosimilar into the market, real-life data coming from the major IBD units in Italy confirm a favorable and confident position on the use of biosimilars in pediatric IBD.
Subject(s)
Biosimilar Pharmaceuticals , Inflammatory Bowel Diseases , Biosimilar Pharmaceuticals/adverse effects , Child , Chronic Disease , Humans , Inflammatory Bowel Diseases/drug therapy , Surveys and QuestionnairesABSTRACT
BACKGROUND: Ileocolonoscopy with histology has been considered the gold standard for Crohn disease (CD) diagnosis and monitoring. Over the last years, magnetic resonance enterography (MRE) has become more and more popular, representing a valid non-invasive technique. OBJECTIVE: To propose a simplified MRE score, the pediatric CD magnetic resonance index (PCDMRI), based only on the most affected bowel segment, to grade active inflammation in children with CD. MATERIALS AND METHODS: Two radiologists retrospectively evaluated MRE images of children with histopathology-proven CD. The PCDMRI was based on six mural and perimural variables assessed for the most affected bowel segment (chosen by visual inspection of the key bowel wall imaging findings associated with active inflammation), and five extramural per-examination features. Correlation analysis was performed between both the PCDMRI and the MRE global score (based on all the affected segments) and the pediatric clinical disease activity index (PCDAI), the simple endoscopic score for CD (SES-CD), serum C-reactive protein (CRP) and fecal calprotectin (fC). Inter-reader reproducibility of the scoring system was estimated. Agreement on disease location between MRE and ileocolonoscopy was evaluated. RESULTS: The study involved 42 children for a total of 80 MRE. PCDMRI and global score positively correlated with PCDAI, SES-CD, CRP and fC. Inter-reader reproducibility was 91%. Agreement on disease location was substantial. CONCLUSION: The PCDMRI and the global score resulted equally correlated with the PCDAI, suggesting a high impact of the most affected segment on symptoms. The PDCMRI may be a useful non-invasive tool for a rapid and reproducible grading of the disease activity in children with ileocolonic CD.
Subject(s)
Colonic Diseases/diagnostic imaging , Crohn Disease/diagnostic imaging , Ileal Diseases/diagnostic imaging , Magnetic Resonance Imaging/methods , Adolescent , Child , Child, Preschool , Colonic Diseases/complications , Crohn Disease/complications , Female , Humans , Ileal Diseases/complications , Male , Retrospective StudiesABSTRACT
Following the spread of the SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) to a global pandemic, concerns have arisen for the disease impact in at-risk populations, especially in immunocompromised hosts. On the other hand, clinical studies have clarified that the COVID-19 clinical burden is mostly due to over-inflammation and immune-mediated multiorgan injury. This has led to downsizing the role of immunosuppression as a determinant of outcome, and early reports confirm the hypothesis that patients undergoing immunosuppressive treatments do not have an increased risk of severe COVID-19 with respect to the general population. Intriguingly, SARS-CoV-2 natural reservoirs, such as bats and mice, have evolved mechanisms of tolerance involving selection of genes optimizing viral clearance through interferon type I and III responses and also dampening inflammasome response and cytokine expression. Children exhibit resistance to COVID-19 severe manifestations, and age-related features in innate and adaptive response possibly explaining this difference are discussed. A competent recognition by the innate immune system and controlled pro-inflammatory signaling seem to be the pillars of an effective response and the premise for pathogen clearance in SARS-CoV-2 infection. Immunosuppression-if not associated with other elements of fragility-do not represent per se an obstacle to this competent/tolerant phenotype in children. Several reports confirm that children receiving immunosuppressive medications have similar clinical involvement and outcomes as the pediatric general population, indicating that maintenance treatments should not be interrupted in suspect or confirmed SARS-CoV-2 infection.
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Objectives: In the era of Coronavirus 2019 (COVID-19), concern has been raised for immunosuppressed patients, including children with inflammatory bowel diseases (IBD). We aimed to collect data from IBD tertiary centers of Lombardy during pandemic. Methods: A cross-sectional survey enrolling IBD children has been completed by seven major IBD centers in Lombardy during lockdown. The clinical form included questions on any symptom consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the IBD adherence treatment. Furthermore, we have reviewed all IBD medical records including new IBD diagnoses and flares in known IBD patients after the lockdown. Results: Questionnaires of 290 IBD children were returned during lockdown. Out of them, 24 children (8%) complained of mild symptoms suspicious of SARS-CoV-2 infection without needing hospitalization or changing IBD treatment. During the lockdown, one patient presented with IBD flare and one had infectious colitis, with no new IBD cases. Conversely, after lockdown, 12/290 (4%) children relapsed and 15 children were newly diagnosed with IBD. Last year, in the same timeframe, 20/300 (7%) children presented with IBD flare, while 17 children had IBD onset with no statistical difference. Conclusions: Our data on children with IBD in a high COVID-19 prevalence region are reassuring. Only a minority of IBD children had mild symptoms, and no hospitalization or treatment modification was needed. Standard IBD treatments including biologics were safely continued. New IBD diagnoses and flares in known IBD children occurred after the lockdown phase, although no significant difference was found compared with the previous year.
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BACKGROUND: Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. METHODS: This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. RESULTS: Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). CONCLUSIONS: Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.
Subject(s)
Celiac Disease , Inflammatory Bowel Diseases , Autoimmune Diseases/complications , Case-Control Studies , Celiac Disease/complications , Child , Colectomy , Colitis, Ulcerative/complications , Crohn Disease/complications , Humans , Inflammatory Bowel Diseases/complications , Phenotype , Puberty, Delayed/etiology , Tumor Necrosis Factor InhibitorsABSTRACT
Background: Very few data regarding the use of infliximab in children with very early-onset inflammatory bowel disease (VEO-IBD) have been reported. Objective: We aimed to assess the efficacy and the safety of infliximab in children with VEO-IBD compared with older children. Methods: Children treated with infliximab were identified within the Italian IBD registry. The primary outcome was the rate of clinical remission at weeks 14 and 54. Secondary outcomes included the proportion of partial clinical response, treatment duration, and incidence of adverse events. Results: Forty-two children with VEO-IBD were compared with 130 children with IBD. Despite significantly higher infliximab withdrawals in VEO-IBD patients during induction (42.9% vs 7.7% p < 0.01), remission rates at week 14 were similar (28.6% vs 43.8%, p = 0.10). At week 54 fewer VEO-IBD children were in remission (15.8% vs 54.3%, p < 0.01). The treatment duration was shorter in VEO-IBD (median 12.0 vs 18.4 months, p < 0.01). During the induction phase, adverse events were more common in the VEO-IBD group (p < 0.01). Conclusion: Compared with older children, VEO-IBD patients have higher rates of infliximab failures, lower remission rates at one year, and more often experience adverse events during induction.