[When and how should small-bowel capsule endoscopy be used in children?] / Quand et comment utiliser la vidéocapsule endoscopique de l'intestin grêle chez l'enfant ?

Small-bowel capsule endoscopy (CE) has recently been used in children. During the past few years, an intense research activity has defined the advantages and limitations of CE. Its uses have been established in several small-bowel pathologies such as obvious or obscure digestive bleeding, Crohn disease, and hereditary polyposis. Although the absence of biopsy reduces the specificity of CE findings, small-bowel exploration using CE achieves better accuracy in detecting lesions than most radiological examinations. In children, swallowing problems and the risk of retention due to stenosis are the main concerns when using CE: these problems can be solved using endoscopic delivery of the capsule and luminal diameter calibration, respectively. This review focuses on the evidence making CE indispensable to small-bowel exploration.

[Mother-to-child transmission of hepatitis B virus despite postexposure prophylaxis: A review of the literature and description of 11 observations]. / Échec de la séroprophylaxie contre le virus de l'hépatite B. Analyse de la littérature et mise au point à partir d'une série de 11 cas de contamination périnatale.

Chronic hepatitis B virus (HBV) infection leads to a risk of developing cirrhosis and hepatocellular carcinoma. In France, where the prevalence of HBV is low, mother-to-child transmission is the cause of chronic infection in more than one-third of cases. After exposure, the risk of chronic infection is the highest for newborns (90 %). The World Health Organization implemented a global immunization program in 1991, applied in France in 1994. A significant number of children are infected each year, however, and failure of postexposure prophylaxis is reported in 4-10 % of newborns. We report 11 children with chronic HBV infection due to failure of serovaccination, followed up in two centers between 1993 and 2015. We discuss maternal screening, serovaccination, and follow-up conditions, as well as the role of maternal viral load, amniocentesis, and mode of delivery as risk factors. These observations confirm that serovaccination failures are related to the nonobservance of recommendations for maternal screening or postexposure prophylaxis, and to a high maternal viral load (>106 copies/mL). We therefore recommend improving the screening strategy, with control of the hepatitis B antigen in early pregnancy, and discussion of treatment with a nucleoside analog during the last trimester of pregnancy. Serovaccination should be enforced. Its efficacy should be controlled when the child reaches 9 months of age, in order to organize the follow-up if infection occurs.

[Food protein-induced enterocolitis syndrome: A case report of diarrhea with hypovolemic shock and methemoglobinemia]. / Syndrome d'entérocolite induite par les protéines alimentaires (SEIPA) : à propos d'une observation de diarrhée avec choc hypovolémique et méthémoglobinémie.

We report on the case of a young infant with chronic diarrhea that worsened and turned into hypovolemic shock with methemoglobinemia. We underline and discuss the main features of food protein-induced enterocolitis syndrome (FPIES). FPIES is a non-IgE-mediated food allergy involving tumor necrosis factor-alpha (TNF-α). Many triggering foods exist but cow's milk, as in the case reported herein, is one of the most frequent. It can start early or be delayed and start around the average age of 5 months. Symptoms are nonspecific with diarrhea and vomiting, but in the presence of methemoglobinemia, the diagnosis must be seriously considered. The oral food challenge remains the gold standard to confirm the diagnosis if there is still a doubt. Treatment of FPIES associates emergency treatment of acute dehydration with the prevention of relapses by avoiding the suspected protein.

[DEFI-ALPHA cohort and POLYGEN DEFI-ALPHA clinical research hospital programme. A study about clinical, biological and genetics factors associated with the occurrence and the evolution of hepatic complications in children with alpha-1 antitrypsin deficiency]. / Cohorte DEFI-ALPHA et projet hospitalier de recherche clinique POLYGEN DEFI-ALPHA. Étude des facteurs cliniques, biologiques et génétiques associés à l'apparition et à l'évolution de complications hépatiques chez les enfants présentant un déficit en alpha-1 antitrypsine.

INTRODUCTION: The alpha-1 antitrypsin (α1-AT) deficiency, most frequently caused by homozygosity for the Z variant (SERPINA1: c.1096 G>A; Glu342Lys), can give rise to two clinical patterns: (i) respiratory impairment with emphysema (mainly in adulthood) because of a pulmonary quantitative defect in anti-elastase activity; (ii) hepatic impairment (mainly in childhood) due to the misfolding of the PiZ protein which accumulates in hepatocytes thus providing cytotoxicity. CURRENT KNOWLEDGE: To date, the clinical and genetic factors responsible for the development of major hepatic injuries (fibrosis and portal hypertension) during childhood in PiZ patients are not known. METHODS: The DEFI-ALPHA cohort, created in 2008, aims to inventory and prospectively study all α1-AT deficient children diagnosed and included after occurrence of a hepatic sign. The POLYGEN DEFI-ALPHA PHRC has recently (2013) been added to the project to identify modifiers genes by two complementary approaches: (i) the candidate genes strategy with the SERPINA1, CFTR (cystic fibrosis gene), MAN1B1 and SORL1 genes, these two latter being implied in the degradation of misfolding proteins; (ii) the whole exome sequencing (WES) strategy in families in which the PiZ proband has a PiZ brother or sister free of any hepatic sign. EXPECTED RESULTS: The clinical parameter we want to explain is the apparition of a portal hypertension in PiZ children. In the DEFI-ALPHA project, three criteria will be tested: (i) age of inclusion in the cohort, (ii) the way of inclusion (neo-natal icterus or later hepatic impairment) and (iii) treatment or not with ursodesoxycholic acid and, if so, its duration. Genetically, polymorphisms on the SERPINA1 and MAN1B1 genes have already been associated in the literature with different clinical evolutions of the A1ATD but very inconstantly. Our study thus aims to confirm or not this association. The CFTR and SORL1 genes have never been studied in the α1-AT deficiency. Finally, the whole exome sequencing strategy could allow the discovery of new unexpected modifiers genes in this disease.

Paediatric liver transplanted patients and prevalence of hepatitis E virus.

BACKGROUND: Hepatitis E is an emerging disease in developed countries and is usually asymptomatic, particularly in children. Chronic infection is possible in immunocompromised individuals. In the context of a liver transplant, it can simulate a rejection. In this case, antiviral therapy may be considered, thus highlighting the need to diagnose hepatitis E virus (HEV) infection in this population. OBJECTIVES: Given the lack of data in France, we have studied the the prevalence of antibodies to HEV in the paediatric liver transplant population. STUDY DESIGN: This was a retrospective study, carried out in Lyon between 1st January 2010 and 31 May 2013. HEV serology (anti-HEV IgM &IgG) and HEV PCR were studied in 96 children who had undergone liver transplants (84 isolated liver and 12 combined liver and kidney transplants). RESULTS: Eight patients (8.3%; 62.5% girls; mean age:12.3 years) were HEV seropositive. The mean period since their transplantation was 10 years (range:2-21.8 years). Biliary atresia was the principal indication for transplantation. Seven of these eight children had received liver transplants. There were no differences between the epidemiological and clinical data concerning these patients and the remainder of the study population, particularly with respect to immunosuppression(7/8 tacrolimus; 50% dual immunosuppression). No cases of chronic hepatitis E were found, but 1/8 had chronic cytolysis(EBV&adenovirus infection). In all the patients tested(4/8), seroconversion had occurred after the transplant. There was no significant differences between the age groups in this study. CONCLUSIONS: This study showed that in France, the prevalence of antibodies to HEV in paediatric liver and combined liver and kidney transplant patients is 8.3%, as has been found by other European authors.

[Is alfa-interferon still current in the management of Kasabach-Merritt syndrome?]. / L'interferon alfa a-t-il encore des indications dans la prise en charge du syndrome de Kasabach-Merrit ?

Kasabach-Merritt syndrome (KMS), characterized by thrombocytopenia, may complicate vascular tumors such as kaposiform hemangioendothelioma and tufted angioma. We report on two infants, respectively 2 months and 15 days old at the onset of symptoms, the first of whom presented with a left cervico-occipito-scapular hemangioma with parotid extension, and the second with a vascular tumor located on the left shoulder with fast extension on the left inferior hemithorax and the left arm. Thrombocytopenia (< 20 G/L) was associated in both cases. Treatment comprised first high-dose corticosteroids (2mg/kg) in association with vincristine (1mg/m(2)/week). Interferon was introduced as third-line treatment at 3 MIU/m(2)/day. In the first patient, interferon was effective both on thrombocytopenia and tumor in 2 months. In the second patient, the first interferon treatment was not effective despite 6 months of therapy. However, a second treatment 8 years later was successful. After 10 and 3 years follow-up, respectively, there were no side effects and most particularly no neurologic complications. These two observations open the discussion of the role of interferon (3 MIU/m(2)/day) as well as new therapies in the control of angiogenesis in case of failure of first-line treatment of complicated KMS vascular tumors.

[Hepatic involvement in hereditary alpha-1-antitrypsin deficiency]. / Atteinte hépatique du déficit héréditaire en alpha-1-antitrypsine.

Apha-1-antitrypsin deficiency is an autosomal recessive genetic disorder seen in all races. The molecular defect is a specific mutation of the SERPINA1 gene leading to synthesis of an abnormal protein (alpha-1-antitrypsin Z) that cannot be secreted and polymerizes in the endoplasmic reticulum of hepatocytes. The inter-individual variability in the responses to intracellular stress induced by the accumulation of abnormal polymers and the mechanisms allowing their degradation is, without doubt, responsible for the different clinical manifestations of the disease. The disease affects the liver where the abnormal protein is synthesized and the lung, which is its place of action. Liver involvement is well recognized in homozygous infants of the phenotype ZZ. In this situation the disease may present a varying picture from neonatal cholestasis (about 15% of neonatal defects) to cirrhosis. However, evolution towards cirrhosis affects less than 3% of infants with the ZZ phenotype and it is preceded in 80% of cases by neonatal cholestasis. In adolescents or adults the manifestations associated with alpha-1-antitrypsin deficiency are usually limited to biochemical abnormalities but may lead to cirrhosis or hepatocellular carcinoma. The hepatic disorder and its complications are treated symptomatically though the pulmonary involvement may benefit from substitution treatment. More specific treatments targeting the molecular and cellular abnormalities are the subject of research.

[Deep vein thrombosis revealing myeloproliferative syndrome in two adolescents]. / Thrombose splanchnique révélatrice d'un syndrome myéloprolifératif chez deux adolescentes.

Deep vein thrombosis occurs in 30% of patients with essential thrombocythemia, but rarely at initial diagnosis. We report two pediatric patients with essential thrombocythemia revealed by atypical deep vein thrombosis. First, a 16-year-old girl presented Budd-Chiari syndrome revealed by a hemorrhagic shock. Clinical exam revealed isolated splenomegaly. A search for thrombophilia found a factor V Leiden homozygous mutation and a Jak2 mutation. Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder. The second case, a 17-year-old girl, had a routine examination by her physician that revealed splenomegaly. Ultrasonography displayed thrombus in the splenic and portal vein. An isolated Jak2 mutation was found and a myeloproliferative disorder was confirmed by bone marrow biopsy. The diagnosis of myeloproliferative disorder was made in both patients presenting atypical venous thrombosis with a Jak2 mutation and confirmed by bone marrow biopsy. These initial presentations of myeloproliferative disorders are rare in childhood and possibly underdiagnosed.

Epstein-Barr virus-associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient.

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

[Helicobacter pylori infection, a classic but often unrecognized cause of iron deficiency anemia in teenagers]. / Anémie ferriprive de l'adolescent liée à une infection àHelicobacter pylori, à propos d'un cas.

We report a case of a 15-year-old teenager who presented with iron deficiency anemia due to Helicobacter pylori infection. Iron deficiency is frequent in infants and during puberty. H. pylori gastritis is a frequent but underdiagnosed cause of refractory anemia. In the case reported herein, the recurrent character of the patient's anemia raised this diagnosis, which was confirmed by endoscopy. Treatment of the H. pylori infection, associated with iron supplementation, successfully corrected the anemia.

[Management of caustic esophagitis in children]. / Prise en charge des enfants après ingestion de substances acides ou alcalines.

In children, caustic ingestion is due to accidents at home and inadequate storage of caustic agents. In emergency, it is useful to remove the soiled clothes, rinse the affected area, and prevent vomiting and feeding. Caustic ingestion (pH<2 or>12) induces burns of the upper gastrointestinal tract requiring esophagogastro-duodenoscopy between H12 and H24. Strong alkalis cause necrosis with liquefaction of the esophagus, penetrating deeply with a high-risk of perforation. Management of these children requires a specialized care center with an intensive care unit, endoscopic equipment, and a surgical team. Esophageal stricture is the main complication; no prophylactic treatment (steroids) is effective. Strictures occur after the 3rd week, and barium swallow should be performed by the end of the 1st month. Stricture are often multiple, long, and tortuous; endoscopic dilatation is difficult with a high-rate of perforation and a low-rate of success. In situ application of mitomycin C or injection of triamcinolone could reduce the recurrence rate of stricture. In recalcitrant or recurrent strictures, it is recommended to perform an esophageal replacement using a colonic interposition or a gastric tube. Endoscopy should also be performed 15-20years after caustic ingestion to screen for early neoplastic lesions. Prevention is very important for avoiding caustic ingestions. Information and education should be given specifically to the parents of toddlers; caustic products should be stored out of reach of children and they should not be kept with food.

[Current indications of ileocolonoscopy in children in 2012]. / Mise au point : évolution des indications de la coloscopie chez l'enfant en 2012.

Indications for ileocolonoscopy were defined in 2002 by the Groupe Francophone d'Hépatologie Gastroentérologie et Nutrition. These recommendations were updated with new data and technical innovations appearing over the last decade. Ileocolonoscopy is primarily indicated for digestive bleeding or anemia and for suspected inflammatory bowel disease. It is now indicated in inflammatory bowel disease for control of mucosal healing after medical treatment and relapse after surgical resection. Iterative ileocolonoscopy is primarily indicated for genetic polyposis and well defined for familial adenomatous polyposis. The contraindications were not modified.

Prevalence of liver complications in children receiving long-term parenteral nutrition.

BACKGROUND/OBJECTIVES: The hepatic prognosis of long-term home total parenteral nutrition (TPN)-dependent children is poorly documented. The objective was to study outcome data in home TPN-dependent children and to describe precisely their liver biopsies in the attempt to analyze risk factors for biochemical and histological hepatic abnormalities. SUBJECTS/METHODS: Medical records of 42 children receiving home TPN for more than 2 years between January 1998 and December 2007 in a single approved home total parenteral center were reviewed. Hepatic biochemical abnormalities were analyzed. Hepatic biopsies were classified by two independent pathologists. RESULTS: Duration of TPN was 7.9±0.8 years (mean±s.e.m.), with an average age at onset of 1.5±0.5 years. A total of 24 patients (57%) developed biochemical liver abnormalities in an average of 2.9±0.4 years after starting TPN. Risk factors for biochemical abnormalities were younger age at TPN commencement, longer duration of TPN, higher rate of catheter-related infections and higher volume and energy content of TPN. Liver biopsies were carried out in 43% of patients (mean age 3.2±0.9 years). Almost all patients had fibrosis (94%). Risk factors were dependent on each histological abnormality: fibrosis was significantly associated with a shorter length of bowel and a longer duration of TPN; cholestasis correlated with a lower percentage of total parenteral energy intake due to lipids; and steatosis had no risk factor identified. CONCLUSION: Our study reports a high rate of histological liver abnormalities and analyzes risk factors in children who underwent very long-term home TPN.

[Granulomatous pulmonary involvement preceding diagnosis of Crohn disease: a pediatric case report]. / Atteinte granulomateuse pulmonaire précédant le diagnostic de maladie de Crohn: à propos d'un cas pédiatrique.

Crohn disease (CD) is a chronic bowel disorder that may affect many other organs such as the eyes, hepatobiliary system, skin, and joints. Pulmonary involvement in association with CD is a classic but uncommon manifestation. It can be primitive with granulomas or secondary to treatments. We report on the case of a teenager in whom the onset of CD was dominated by respiratory symptoms. Because of this presentation, we also suspected opportunistic infections such as tuberculosis and other granulomatous pulmonary diseases such as sarcoidosis or hypersensitivity pneumonitis.

Prevention of relapse by mesalazine (Pentasa) in pediatric Crohn's disease: a multicenter, double-blind, randomized, placebo-controlled trial.

AIM: This study aimed to test the efficacy of mesalazine in maintaining remission in pediatric Crohn's disease (CD) following successful flare-up treatment. METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year. Treatment allocation was stratified according to flare-up treatment (nutrition or medication alone). Recruitment was carried out over two periods, as the first period's results showed a trend favoring mesalazine. Relapse was defined as a Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35) in the mesalazine and placebo groups, respectively. We demonstrated a twofold lower relapse risk (P<0.02) in patients taking mesalazine in the medication stratum (first recruitment period), and a twofold higher risk in patients taking mesalazine in the nutrition stratum (second recruitment period), compared with the other groups. None of the children's characteristics, which differed across the two recruitment periods, accounted for the between-period variation in mesalazine efficacy. One serious adverse event was reported in each treatment group. CONCLUSION: Overall, mesalazine does not appear to be an effective maintenance treatment in pediatric CD.