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OBJECTIVES: Pediatric autoimmune pancreatitis (P-AIP) is an uncommon disease whose diagnosis requires strong clinical suspicion. Late diagnosis increases morbidity. We aimed to compare the usefulness of the 2011 International Consensus Diagnostic Criteria (ICDC) for Autoimmune Pancreatitis with the 2018 INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) criteria. METHODS: We retrospectively analyzed demographics and clinical, laboratory, radiological, and histological findings at diagnosis and during long-term follow-up in children diagnosed with AIP in 2 tertiary hospitals between 2008 and 2021. RESULTS: We included 11 patients [6 girls; median age at diagnosis, 12.5 (range 2.8-15.7) years]. The most common symptom was abdominal pain. Pancreatic enzymes were elevated in 10 patients, and serum immunoglobulin G4 was elevated in 1. Magnetic resonance imaging showed enlargement of the pancreatic head in 10 patients and general pancreatic enlargement in 1. Pancreatic and papilla tissue were obtained from 9 patients. All patients received corticosteroids (prednisolone), and 4 also received azathioprine. According to the ICDC, all patients were classified as probable or non-otherwise specified AIP. According to INSPPIRE criteria, all patients were classified as AIP. Using the INSPPIRE criteria would have avoided biopsies in 6 patients who responded well to corticosteroids. CONCLUSIONS: The INSPPIRE criteria are useful. Using the ICDC in pediatric patients can delay diagnosis and result in unnecessary invasive tests.
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Doenças Autoimunes , Pancreatite Autoimune , Feminino , Humanos , Criança , Pré-Escolar , Adolescente , Pancreatite Autoimune/diagnóstico , Estudos Retrospectivos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Diagnóstico Diferencial , Corticosteroides/uso terapêuticoRESUMO
Vedolizumab is a humanised monoclonal antibody that binds to integrin α4ß7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease; however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-α) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with CD and 75% of those with UC; p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC; p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively; p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively; p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were uncommon and mild. Three patients (7.1%) presented headaches, 1 presented alopecia, 1 presented anaemia and 1 presented dermatitis.Conclusion: The results show that treatment with vedolizumab is a safe and effective option for achieving clinical remission in paediatric patients with inflammatory bowel disease with primary failure or loss of response to other treatments, especially in UC. What is Known: ⢠Vedolizumab is effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. ⢠Most studies and clinical trials have been performed on adult populations, and there is currently no indication for paediatric populations. What is New: ⢠Children with inflammatory bowel disease refractory to anti-TNF presented higher clinical remission rates than those published for adults. ⢠There are few publications of this magnitude on paediatric populations treated with vedolizumab and with long-term follow-up (52 weeks).
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Adolescente , Anticorpos Monoclonais Humanizados , Criança , Colite Ulcerativa/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose TumoralRESUMO
BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing. OBJECTIVE: The aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance. METHODS: This observational and ambispective single-centre study was conducted in paediatric patients with IBD treated with infliximab between July 2016 and July 2022 in the Paediatric Gastroenterology Service of the Hospital Universitari Vall d'Hebron (HUVH) (Spain). Demographic, clinical, and analytical variables were collected. Twenty SNPs potentially associated with variations in the response to infliximab plasma concentrations were analysed. infliximab serum concentrations and antibodies to infliximab (ATI) were determined by ELISA. PopPK modelling was performed using nonlinear mixed-effects analysis (NONMEM). RESULTS: Thirty patients (21 males) were included. The median age (range) at the start of infliximab treatment was 13 years (16 months to 16 years). A total of 190 samples were obtained for model development (49 [25.8%] during the induction phase). The pharmacokinetics (PK) of infliximab were described using a two-compartment model. Weight, erythrocyte sedimentation rate (ESR), faecal calprotectin (FC), and the SNP rs1048610 (ADAM17) showed statistical significance for clearance (CL), and albumin for inter-compartmental clearance (Q). Estimates of CL1 (genotype 1-AA), CL2 (genotype 2-AG), CL3 (genotype 3-GG), Q, Vc, and Vp (central and peripheral distribution volumes) were 0.0066 L/h/46.4 kg, 0.0055 L/h/46.4 kg, 0.0081 L/h/46.4 kg, 0.0029 L/h/46.4 kg, 0.6750 L/46.4 kg, and 1.19 L/46.4 kg, respectively. The interindividual variability (IIV) estimates for clearance, Vc, and Vp were 19.33, 16.42, and 36.02%, respectively. CONCLUSIONS: A popPK model utilising weight, albumin, FC, ESR, and the SNP rs1048610 accurately predicted infliximab trough concentrations in children with IBD.
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Biomarcadores , Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais , Infliximab , Polimorfismo de Nucleotídeo Único , Humanos , Infliximab/farmacocinética , Infliximab/uso terapêutico , Criança , Masculino , Adolescente , Feminino , Pré-Escolar , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Lactente , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/uso terapêutico , Modelos Biológicos , EspanhaRESUMO
Background and Aims: Diagnostic delay (DD) is especially relevant in children with inflammatory bowel disease, leading to potential complications. We examined the intervals and factors for DD in the pediatric population of Spain. Methods: We conducted a multicentric prospective study, including 149 pediatric inflammatory bowel disease patients, obtaining clinical, anthropometric, and biochemical data. Time to diagnosis (TD) was divided into several intervals to identify those where the DD was longer and find the variables that prolonged those intervals. Missed opportunities for diagnosis (MODs) were also identified. Results: Overall TD was 4.4 months (interquartile range [IQR] 2.6-10.4), being significantly higher in Crohn's disease (CD) than in ulcerative colitis (UC) (6.3 [IQR 3.3-12.3] vs. 3 [IQR 1.6-5.6] months, p = 0.0001). Time from the visit to the first physician until referral to a pediatric gastroenterologist was the main contributor to TD (2.4 months [IQR 1.03-7.17] in CD vs. 0.83 months [IQR 0.30-2.50] in UC, p = 0.0001). One hundred and ten patients (78.3%) visited more than one physician (29.9% to 4 or more), and 16.3% visited the same physician more than six times before being assessed by the pediatric gastroenterologist. The number of MODs was significantly higher in CD than that in UC patients: 4 MODs (IQR 2-7) vs. 2 MODs ([IQR 1-5], p = 0.003). Referral by pediatricians from hospital care allowed earlier IBD diagnosis (odds ratio 3.2 [95% confidence interval 1.1-8.9], p = 0.025). Conclusions: TD and DD were significantly higher in CD than those in UC. IBD patients (especially those with CD) undergo a large number of medical visits until the final diagnosis.
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Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (µg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 µg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.
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Doença de Crohn/terapia , Nutrição Enteral , Adolescente , Criança , Doença de Crohn/diagnóstico , Doença de Crohn/metabolismo , Feminino , Humanos , Masculino , Indução de Remissão , Estudos RetrospectivosRESUMO
INTRODUCTION: Rumination syndrome is an uncommon gastrointestinal functional disorder that may be difficult to diagnose, as not many physicians are aware of this condition. In many cases, patients undergo numerous tests and are prescribed several treatments based on erroneous diagnoses. When the correct diagnosis is eventually made, therapy for the syndrome can be difficult and complex because of its multifactorial nature. The aim of this study was to present our experience with this condition, by presenting an analysis of the clinical, diagnostic, and therapeutic data of our patients. PATIENTS AND METHOD: A prospective and retrospective study was conducted on all cases of rumination syndrome diagnosed between January 2010 and May 2016 in patients attending the Paediatric Gastroenterology Departments of two hospitals: Consorci Sanitari de Terrassa and Hospital Materno-Infantil Vall d'Hebron (Barcelona, Spain). RESULTS: The analysis included 12 patients, with a mean age at the onset of symptoms of 9 years and 1 month, and the mean time period to make the diagnosis was 2 years and 3 months. A mean of 8.1 complementary tests were carried out before establishing the diagnosis. In 10 of the 12 patients, some type of treatment had been given before the diagnosis of rumination syndrome, but was unsuccessful in all cases. Ten of our patients underwent the novel, experimental biofeedback therapy. CONCLUSIONS: Due to the limited knowledge of this condition among attending professionals in terms of the clinical presentation, diagnosis, and treatment, patients with rumination syndrome are often misdiagnosed and undergo numerous avoidable complementary tests, and invasive, costly treatments.
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Transtornos de Alimentação na Infância/diagnóstico , Transtornos de Alimentação na Infância/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , SíndromeRESUMO
Chylomicron retention disease, also known as Anderson's disease, is a rare hereditary hypocholesterolemic disorder, recessive inherited, characterized by nonspecific symptoms as abdominal distension, steatorrhea, and vomiting associated with failure to thrive. We describe a patient with failure to thrive, chronic diarrhea and steatorrhea who the diagnosis of chylomicron retention disease was established after several months of disease progression. The genetic study confirmed a homozygosity mutation in SAR1B gene, identifying a mutation never previous described [c.83_84delTG(p.Leu28Argfs*7)]. With this case report the authors aim to highlight for this very rare cause of failure to thrive and for the importance of an attempting diagnosis, in order to start adequate management with low fat diet supplemented with fat-soluble vitamins, reverting the state of malnutrition and avoiding possible irreversible and desvantating complications.
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INTRODUCTION: Food allergy is an increasing health problem in the developed world. Cow's milk protein is the main cause of food allergy in infants. Without an appropriate diagnostic workup, there is a high risk of both over- and underdiagnosis and therefore, over and undertreatment. The objective of our study was to analyze the variability in cow's milk protein allergy (CMPA) management by pediatric gastroenterologists in Spain. METHODS: A fifty item questionnaire, including open and closed items in a Likert's scale from 0 to 5, was drafted and distributed through the Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) e-mail list. RESULTS: Seventy-three questionnaires were received back out of 321. Only 3 of the items achieved concordance greater than 90%. Thirty-three percent considered oral challenge to be necessary for the diagnosis of CMPA under any circumstance. Twenty-five percent considered that symptom improvement after cow's milk removal was enough for the diagnosis. Oral challenge was performed at home by 83.5% in non-IgE mediated cases. Extensively hydrolyzed casein formulas were the treatment of choice for 69.9%. Soy formulas were the last option. Almost all respondents were aware of the existence of clinical guidelines on CMPA, being European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines the most followed (64.4%). Twenty-three percent considered that their knowledge about allergy was inadequate. CONCLUSIONS: Although CMPA is a prevalent condition that pediatric gastroenterologists have been treating for decades, we found a huge variability on its management. There is potential for improvement in this field among pediatric gastroenterologist in the future.