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OBJECTIVES: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. METHODS: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. RESULTS: Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received before stricture diagnosis included MODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). CONCLUSION: In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.
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Enfermedad de Crohn , Intestino Delgado , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Masculino , Estudios Retrospectivos , Femenino , Factores de Riesgo , Niño , Intestino Delgado/cirugía , Intestino Delgado/patología , Adolescente , Constricción Patológica/etiología , Francia , Imagen por Resonancia Magnética , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugíaRESUMEN
BACKGROUND: Percutaneous endoscopic gastrostomy is commonly used for enteral nutritional access, but gastrocutaneous fistulae (GCF) may persist after tube removal, posing clinical challenges. The use of endoscopic closure devices, including over-the-scope clips (OTSC), has shown promise in managing non-healing fistulae, although data in the pediatric population are limited. METHODS: A retrospective multicenter study analyzed pediatric patients who underwent GCF closure following gastrostomy tube removal. Data from seven centers across multiple countries were collected, including patient demographics, procedural details, complications, and outcomes. Closure techniques were compared between OTSC and surgical closure. RESULTS: Of 67 pediatric patients included, 21 underwent OTSC closure and 46 had surgical closure. Surgical closure demonstrated a higher success rate (100%) compared to OTSC closure (61.9%, P < 0.001). While procedural duration was shorter for OTSC closure (25 vs. 40 min, P = 0.002), complications, and scar quality were comparable between techniques. A subsequent sub-analysis did not reveal differences based on center experience. CONCLUSION: OTSC closure is feasible and safe in pediatric patients, but surgical closure remains superior in achieving sustained GCF closure, although OTSC offers benefits, such as shorter procedural duration, potentially reducing the duration of general anesthesia exposure. Non-operative approaches, including OTSC, may be a valuable alternative to surgical closure.
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OBJECTIVE: The DSM-5 classification introduced new Feeding and Eating Disorders (FED) diagnostic categories, notably Avoidant and Restrictive Food Intake Disorder (ARFID), which, like other FED, can present psychiatric and gastrointestinal symptoms. However, paediatric clinical research that focuses on children below the age of 12 years remains scarce. The aim of this study was first to investigate the clinical features of FED in a cohort of children, second to compare them according to their recruitment (gastroenterology or psychiatry unit). METHOD: This non-interventional retrospective cohort study analysed 191 patients in a French paediatric tertiary care centre (gastroenterology n = 100, psychiatry n = 91). The main outcome variables were clinical data (type of FED, BMI, nutritional support, chronic diseases, psychiatric comorbidities, sensory, sleep, language disorders, gastrointestinal complaints, adverse life events, family history). The outcome was defined by a Clinical Global Impression of Change-score. RESULTS: FED diagnoses were ARFID (n = 100), Unspecified FED (UFED, n = 57), anorexia nervosa (AN, n = 33) and one pica/rumination. Mean follow-up was 3.28 years (SD 1.91). ARFID was associated with selective and sensory disorders (p < 0.001); they had more anxiety disorders than patients with UFED (p < 0.001). Patients with UFED had more chewing difficulties, language disorder (p < 0.001), and more FED related to chronic disease (p < 0.05) than patients with ARFID and AN. Patients with AN were female, underweight, referred exclusively to the psychiatrist, and had more depression than patients with ARFID and UFED (p < 0.001). The gastroenterology cohort included more UFED, while the psychiatry cohort included more psychiatric comorbidities (p < 0.001). A worse clinical outcome was associated with ARFID, a younger age at onset (p < 0.001), selective/sensory disorders and nutritional support (p < 0.05). CONCLUSION: ARFID and UFED children were diagnosed either by gastroenterologists or psychiatrists. Due to frequently associated somatic and psychiatric comorbidities, children with FED should benefit from a multidisciplinary assessment and care.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Gastroenterología , Humanos , Femenino , Niño , Masculino , Estudios Retrospectivos , Estudios de Cohortes , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Trastornos de la Sensación , Ingestión de AlimentosRESUMEN
INTRODUCTION: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. METHODS: All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. RESULTS: Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. DISCUSSION: Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.
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Enfermedad de Crohn , Fisura Anal , Fístula Rectal , Femenino , Niño , Humanos , Adolescente , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/diagnóstico , Estudios de Seguimiento , Estudios Retrospectivos , Fisura Anal/etiología , Fisura Anal/complicaciones , Fístula Rectal/etiologíaRESUMEN
INTRODUCTION: We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). RESULTS: A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). DISCUSSION: In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.
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Colitis Ulcerosa , Niño , Humanos , Femenino , Adolescente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/diagnóstico , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Colectomía , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.
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Pancreatitis Crónica , Tripsinógeno , Humanos , Alelos , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad , Genotipo , Mutación , Pancreatitis Crónica/genética , Tripsina/genética , Tripsinógeno/genéticaRESUMEN
OBJECTIVES: Ustekinumab is known to be efficient in adult patients suffering from moderate to severe Crohn disease (CD) and ulcerative colitis (UC) resistant to anti-tumor necrosis factor-alpha (TNF-α). Here, we described the clinical course of treatment with ustekinumab in French pediatric inflammatory bowel disease (IBD) patients treated with ustekinumab. METHODS: This study includes all pediatric patients treated by ustekinumab injection for IBD (CD and UC), between January 2016 and December 2019. RESULTS: Fifty-three patients were enrolled, 15 males and 38 females. Forty-eight patients (90%) had a diagnosis of CD and 5 (9.4%) had UC. Sixty-five percent of CD patients presented an ileocolitis. Perineal disease was observed in 20 out of 48 CD patients (41.7%), among them 9 were treated surgically. All patients included were resistant to anti-TNF-α treatment. Fifty-one percent had presented side effects linked to anti-TNF-α, including psoriasis and anaphylactic reaction. The average Pediatric Crohn Disease Activity Index (PCDAI) at induction was 28.7 (5-85), 18.7 (0-75) at 3 months of treatment and 10 (0-35) at the last follow-up. The average Pediatric Ulcerative Colitis Activity Index at induction was 47 (25-65), 25 (15-40) at 3 months of treatment and 18.3 (0-35) at the last follow-up. No severe side effects were observed. CONCLUSION: In this retrospective, multicentral study, ustekinumab proved to be efficient in pediatric patients resistant to anti-TNF-α. PCDAI has been significantly improved in patients with severe disease, treated with ustekinumab.
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Colitis Ulcerosa , Enfermedad de Crohn , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Inflamatorias del Intestino , Masculino , Adulto , Femenino , Humanos , Niño , Ustekinumab/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: We evaluated the impact of immunosuppressants (IS) and anti-tumor necrosis factor (TNF) introduction on Crohn's disease (CD) long-term outcomes in a large population-based, pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of CD occurring when they were younger than age 17 years and between 1988 and 2011 were followed up retrospectively until 2013. Three diagnostic periods were defined: 1988 to 1993 (period [P]1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). Medication exposure and disease outcomes were compared between the 3 diagnostic periods. RESULTS: A total of 1007 patients diagnosed with CD were followed up for a median duration of 8.8 years (interquartile range, 4.6-14.2 y). The IS and anti-TNF exposure rate at 5 years increased over time from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3), respectively. In parallel, the risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P = .0003, Ptrend < .0001), and between the pre-anti-TNF era (P1 + P2, 32%) and the anti-TNF era (P3, 22%) (P = .0007). The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%; P = .11, Ptrend = .041) and between the pre-anti-TNF era (P1 + P2, 28%) and the anti-TNF era (P3, 20%) (P = .040). The risk for a CD flare-related hospitalization at 5 years remained stable over time (P1, 31%; P2, 31%; and P3, 29%; P = .76, Ptrend = .53). CONCLUSIONS: In parallel with the increased use of IS and anti-TNF, positive changes in the natural history of pediatric-onset CD were observed at the population level. A decreased risk of both intestinal resections and stricturing complications were observed during the anti-TNF era.
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Enfermedad de Crohn , Procedimientos Quirúrgicos del Sistema Digestivo , Niño , Humanos , Adolescente , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/diagnóstico , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral , Inmunosupresores/uso terapéuticoRESUMEN
Appetite traits have multifactorial origins. In association with environmental and genetic factors, they could become problematic and lead to Feeding or Eating Disorders (FED). As the DSM-5 classification is not suitable for pediatric FED, another way to describe eating behavior is to distinguish the clinical profiles of "small eater" and "big eater". The aim of this study was to identify socio-demographic and medical factors associated with these profiles, and to compare problematic and non-problematic profiles. From the Pedianut study, we analyzed socio-demographic, medical and family history data among 401 children according to 4 age groups (<1 year n = 101, 1-6 years n = 99, 6-12 years n = 100, 12-18 years n = 101). The information collected on eating behavior made it possible to define small eater profile (SEP) and big eater profile (BEP) using predefined grids. BEP was more frequent in adolescents (35.6%), and SEP was more frequent in children aged 1-6 years (34.3%). BEP was associated with having separated parents, being male and the oldest sibling (p < 0.05). Problematic BEP was associated with eating while watching television, being a girl, and having sensory disorders (p < 0.05). SEP was associated, whatever age, with non-breastfeeding, chronic illness, psychological history, sensory disorders, language delays (in the 1-6 year age group), and family history of FED (in the adolescent group) (p < 0.05). This analysis of factors associated with eater profile opens new perspectives for research on risk factors associated with eating traits, which warrants further study in larger populations to delineate transition from healthy to problematic eating.
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Conducta Alimentaria , Trastornos de Alimentación y de la Ingestión de Alimentos , Adolescente , Niño , Estudios de Cohortes , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Femenino , Humanos , Lactante , Masculino , Encuestas y CuestionariosRESUMEN
PURPOSE: Avoidant restrictive food intake disorder (ARFID) was recently characterized, according to the DSM-5 classification, as a feeding and eating disorder (FED). However, ARFID remains poorly known by most pediatricians, but also by psychiatrists and primary care professionals. Despite the fact that patients with ARFID generally have a higher BMI than patients with anorexia nervosa, our purpose was to highlight the fact that they may present severe nutritional deficiencies and major somatic complications when the diagnosis is delayed. METHOD: We describe here a case of a 16-year-old boy who presented with severe undernutrition (BMI = 11.5) leading to Ogilvie's syndrome, which resolved with enteral refeeding. Because of undernutrition, very bad dental condition, and encopresis, some physicians wrongly suspected child neglect, but retrospective analysis of his personal history revealed a long-term FED and sensory specificities that led to the final diagnosis of an ARFID-autism spectrum disorder (ASD) association. A literature review was conducted on the ARFID somatic complications. CONCLUSION: The training of health professionals in the clinical forms of pediatric FED, including ARFID, is necessary, to promote early diagnosis and prevent poor nutritional outcomes. In this case the association of ARFID-ASD and the delay in access to specialized care favored by the disadvantaged social environment led to severe gastrointestinal complications. LEVEL OF EVIDENCE: V, descriptive study.
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Trastorno del Espectro Autista , Trastorno de la Ingesta Alimentaria Evitativa/Restrictiva , Seudoobstrucción Colónica , Trastornos de Alimentación y de la Ingestión de Alimentos , Desnutrición , Adolescente , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/diagnóstico , Niño , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Humanos , Masculino , Estudios RetrospectivosRESUMEN
PURPOSE: Avoidant Restrictive Food Intake Disorder (ARFID) was recently characterized in the DSM-5 classification. Potential differential diagnoses remain poorly reported in the literature. Our purpose was to present a possible Munchausen syndrome by proxy with undernutrition and scurvy, presenting as ARFID in a child. METHODS: We describe here a case of an 8-year-old boy who presented with severe undernutrition (BMI = 11.4) and scurvy leading to joint pains. The boy had had a very selective diet since early childhood, and his condition required hospitalization and enteral refeeding. Because of his specific eating behaviour, an ARFID was initially suspected. However, observation of the mother-child relationship, analysis of the child's eating behaviour, and retrospective analysis of his personal history suggested that this was not a true ARFID, and that the selective eating behaviour had probably been induced by the mother over many years, who probably maintained a low variety diet. CONCLUSION: Munchausen syndrome by proxy is a difficult differential diagnosis, which may also affect patients with ARFID symptoms, which may also present in the affected child as apparent ARFID. LEVEL OF EVIDENCE: Level V, descriptive study.
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Anorexia Nerviosa , Trastorno de la Ingesta Alimentaria Evitativa/Restrictiva , Trastornos de Alimentación y de la Ingestión de Alimentos , Síndrome de Munchausen Causado por Tercero , Escorbuto , Masculino , Femenino , Humanos , Preescolar , Niño , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Anorexia Nerviosa/diagnóstico , Estudios Retrospectivos , Escorbuto/complicaciones , Escorbuto/diagnóstico , Síndrome de Munchausen Causado por Tercero/diagnósticoRESUMEN
OBJECTIVES: Crohn disease (CD) can affect patient's quality of life (QOL) with physical, social, and psychological impacts. This study aimed to investigate the QOL of children with CD and its relationship with patient and disease characteristics. METHODS: Children ages from 10 to 17 years with diagnosed CD for more than 6 months were eligible to this cross-sectional study conducted in 35 French pediatric centers. QOL was assessed by the IMPACT-III questionnaire. Patient and disease characteristics were collected. RESULTS: A total of 218 children (42% of girls) were included at a median age of 14 years (interquartile range [IQR]: 13--16). Median duration of CD was 3.2 years (IQR: 1.7-5.1) and 63% of children were in clinical remission assessed by wPCDAI. Total IMPACT-III score was 62.8 (±11.0). The lowest score was in "emotional functioning" subdomain (mean: 42.8â±â11.2). Clinical remission was the main independent factor associated with QOL of children with CD (5.74 points higher compared with those "with active disease", 95% confidence interval [CI] 2.77--8.70, Pâ<â0.001). Age of patient at the evaluation was found negatively correlated with QOL (-0.76 per year, 95% CI: -1.47 to -0.06, Pâ=â0.009). Presence of psychological disorders was associated with a lower QOL (-9.6 points lower to those without, 95% CI: -13.34 to -5.86, Pâ<â0.0001). Total IMPACT-III and its subdomains scores were not related to sex, disease duration, or treatments. CONCLUSIONS: These results not only confirm that clinical remission is a major issue for the QOL of patients, but also highlights the importance of psychological care.
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Enfermedad de Crohn , Calidad de Vida , Adolescente , Niño , Enfermedad de Crohn/terapia , Estudios Transversales , Emociones , Femenino , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Episodic angioedema with eosinophilia (EAE, Gleich syndrome) is a rare disease, consisting of recurrent angioedema with hypereosinophilia and frequent increased serum immunoglobulin M levels. Less than 100 patients have been reported, mainly adults, sometimes with underlying lymphocytic variant of hypereosinophilic syndrome (HESL ). The aim of this study was to identify and describe pediatric cases. METHODS: We performed a retrospective study of all pediatric cases of EAE referred within the French National Referral Center for Hypereosinophilic Syndrome (CEREO). Next, the PRISMA guidelines were applied in order to perform a systematic review (data sources: PubMed, Web of Science). RESULTS: Among the two reported and 15 previously published cases of EAE occurring in children, the main clinical findings mimicked those of adults, including recurrent angioedema, hives, and weight gain. The median time between the first angioedema flare and the diagnosis of EAE was 5 years in published cases. Hypereosinophilia was constant, usually worsening with each attack, but seldom disappeared between flares. Total IgM serum levels were elevated in 16 patients. Four children had evidence of abnormal CD3- CD4+ T cells. First-line therapy relied on oral corticosteroids in all patients, and further lines (used in five patients) included interferon-α, methotrexate, and cyclosporin. Two children developed eosinophilic myocarditis during follow-up. CONCLUSION: Pediatricians should be aware that EAE is a diagnosis to consider in children. T-cell immunophenotyping is warranted in this setting. Prognosis seems fair, yet eosinophil-related organ damage may occur in patients with persistent eosinophilia.
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Angioedema/complicaciones , Eosinofilia/complicaciones , Adolescente , Corticoesteroides/uso terapéutico , Angioedema/diagnóstico , Angioedema/tratamiento farmacológico , Niño , Preescolar , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Eosinófilos/inmunología , Femenino , Humanos , Síndrome Hipereosinofílico/complicaciones , Inmunoglobulina M/sangre , Inmunofenotipificación , Masculino , Miocarditis/complicaciones , Recurrencia , Estudios Retrospectivos , Linfocitos T/inmunología , Resultado del Tratamiento , Urticaria/complicacionesRESUMEN
OBJECTIVES: Neurological adverse effects (NAEs) induced by biotherapies have been reported in the literature mainly in adult patients with inflammatory bowel disease (IBD), rheumatic diseases, or psoriasis. There are scant data in children. Aims of this study are to report and describe noninfective NAE associated with anti-TNFα antibodies in pediatric IBD, and to evaluate their incidence. METHODS: We retrospectively collected all reports of NAE in pediatric IBD treated with anti-TNFα antibodies recorded in the French Pharmacovigilance Database. To estimate the national incidence of NAEs, we extrapolated data from the French regional inception population-based cohort EPIMAD. RESULTS: Between 2000 and 2018, 231 adverse events in pediatric IBD exposed to anti-TNFα antibodies were reported to this Database. Seventeen NAEs (7.36%) were collected: 8 severe NAE (1 demyelinating neuropathy, 1 optic neuritis, 1 acute transverse myelitis, 1 polyradiculoneuritis, 1 sensorineural hearing loss, 1 seizure, 1 stroke, and 1 glioma), 7 moderate NAE (headaches), and 2 neuropsychic events. The median delay between anti-TNFα start and NAE occurrence was 6 months (range: 13 days to 26 months). In 10 of 17 patients, anti-TNFα antibodies were stopped. Nine of 17 patients had a complete resolution (including 2 severe NAE) and 8 of 17 a partial resolution (including 6 severe NAE). We estimate the incidence of severe NAE in pediatric IBD treated with anti-TNFα antibodies at 1 case for 10,000 patients-year in France. CONCLUSIONS: NAE associated with anti-TNFα antibodies in pediatric IBD are rare. In severe NAE, we recommend to discontinue anti-TNFα therapy and to consider alternative treatment.
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Enfermedades Inflamatorias del Intestino , Psoriasis , Adalimumab/efectos adversos , Adulto , Niño , Francia , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/efectos adversos , Estudios Retrospectivos , Factor de Necrosis Tumoral alfaRESUMEN
Ustekinumab is approved for the treatment of psoriasis in adolescents and for the treatment of moderate to severe Crohn's disease (CD) in adults, but data are lacking in pediatric CD. We report a case of severe psoriasis induced by biotherapies in an adolescent with CD that improved after switching to ustekinumab (90 mg at weeks 0, 2, and 4 and then every 8 weeks). The patient had not experienced CD relapse after 1 year of follow-up. Ustekinumab can be an alternative therapy for psoriasis induced by biotherapies when conventional treatment fails and can maintain remission of CD.
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Terapia Biológica/efectos adversos , Enfermedad de Crohn/terapia , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Ustekinumab/uso terapéutico , Adolescente , Femenino , Humanos , Psoriasis/etiología , Inducción de Remisión , Piel/patologíaRESUMEN
OBJECTIVE: To study the prevalence of Barrett esophagus (BE) (gastric and/or intestinal metaplasia) in adolescents treated for esophageal atresia (EA). SUMMARY OF BACKGROUND DATA: EA patients are at high risk of BE. METHODS: This multicenter prospective study included EA patients aged 15 to 19 years. All eligible patients were proposed an upper endoscopy with multistaged esophageal biopsies under general anesthesia. Histological suspicion of metaplasia was confirmed centrally. RESULTS: One hundred twenty patients [mean age, 16.5 years (±1.4)] were included; 70% had been treated for gastroesophageal reflux disease (GERD) during infancy. At evaluation, 8% were undernourished, 41% had received antireflux surgery, and 41% presented with GERD symptoms, although only 28% were receiving medical treatment. Esophagitis was found at endoscopy in 34% and confirmed at histology in 67%. BE was suspected after endoscopy in 37% and was confirmed by histology for 43% of patients (50 gastric and 1 intestinal metaplasia). No endoscopic or histological anomalies were found at the anastomosis site. BE was not significantly related to clinical symptoms. In multivariate analysis, BE was associated with EA without fistula (P = 0.03), previous multiple antireflux surgery (P = 0.04), esophageal dilation (P = 0.04), suspicion of BE at endoscopy (P < 0.001), and histological esophagitis (P = 0.02). CONCLUSIONS: Patients with EA are at high risk of persistent GERD and BE. The development of BE is related to GERD history. Long-term systematic follow-up of the esophageal mucosa including multistaged biopsies is required, even in asymptomatic patients. (NCT02495051).
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Esófago de Barrett/epidemiología , Atresia Esofágica/cirugía , Adolescente , Biopsia , Esofagitis/complicaciones , Esofagoscopía , Femenino , Francia/epidemiología , Reflujo Gastroesofágico/complicaciones , Humanos , Masculino , Prevalencia , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. RESULTS: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. CONCLUSION: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adolescente , Niño , Femenino , Humanos , Adulto Joven , Adalimumab/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND AND AIMS: Paediatric-onset IBD [pIBD] is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer. METHODS: All patients diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] before the age of 17 years between 1988 and 2011 in the EPIMAD registry were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence [SIR] and mortality ratios [SMR] were estimated compared to the general population. Cox regression was used to compare the effect of exposures on cancer and mortality among IBD patients. RESULTS: We included 1344 patients [52% males, 75% CD], totalling 12 957 patient-years for cancer incidence and 18 817 patient-years for mortality. There were 14 cases of cancer [median age 27.8 years] and 15 deaths [median age 28.8 years]. The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIRâ =â 2.7 (95% confidence interval [CI]: 1.5-4.8), SMRâ =â 1.7 [95% CI: 1.0-2.8]. Colorectal cancer had the highest SIR and SMR: SIRâ =â 41.2 [95% CI: 17.2-99.0], SMRâ =â 70.4 [95% CI 22.7-218.2]. Cancer was associated with (hazard ratio [HR], 95% CI): active smoking at diagnosis [5.5, 1.8-16.5], pâ =â 0.002; any exposure to anti-tumour necrosis factor [6.1, 1.7-22.3], pâ =â 0.0065; and exposure to combination therapy [7.4, 1.8-29.7], pâ =â 0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 [95% CI: 1.7-13.8], pâ =â 0.003). CONCLUSIONS: In this large population-based cohort, patients with pIBD had an increased risk of both cancer [2.7-fold] and mortality [1.7-fold], particularly for colorectal cancer.
Asunto(s)
Colitis Ulcerosa , Neoplasias Colorrectales , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Masculino , Niño , Humanos , Adulto , Adolescente , Femenino , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Incidencia , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiologíaRESUMEN
Background: Chronic constipation is common in children and often requires prolonged laxative treatment. Preliminary studies suggest that the probiotic Limosilactobacillus reuteri (L. reuteri) may be useful in treating constipation in children, but these preliminary results need to be replicated. The objective of this study was to assess the efficacy of L. reuteri in infants and young children with chronic functional constipation. Methods: A prospective double-blind randomized placebo-controlled trial was conducted in 5 pediatric departments in France between June 2017 and June 2021. In all, 49 patients-ages 6 months to 4 years, and suffering from chronic constipation per Rome IV criteria-were randomly allocated to the test and control groups. For 4 weeks, all were orally administered 5 daily drops of the test (L. reuteri DSM 17938 at 108 colony-forming units per day) or control (placebo) treatment, respectively. Participants were clinically assessed at 4 and 8 weeks. Parents were asked to daily record the number of spontaneous bowel movements (SBMs), stool consistency, and the use of any additional laxatives. Informed consent was obtained from parents of all recruited patients, and the study was approved by both an ethics committee and the French National Agency for Medicines and Health Products Safety (ANSM). The study is registered on ClinicalTrials.gov (NCT03030664). Results: The change in SBMs relative to baseline was greater in the control group at week 4 (control: 0.27 ± 0.5; test: 0.23 ± 0.5; P = 0.01) and in the test group at week 8 (control: 0.26 ± 0.4; test: 0.22 ± 0.5; P = 0.03). At week 4, the groups did not differ in number of responders (≥3 stools per week, with no non-retentive fecal incontinence), use of rescue medication, scoring of pain during defecation (Faces Pain Scale-Revised), or stool consistency (Bristol Stool Form Scale). Conclusion: This double-blind randomized controlled trial did not confirm the efficacy of L. reuteri for treatment of chronic functional constipation in young children.