[Knowledge of adolescents with inflammatory bowel disease: Results of a multicenter cross-sectional survey]. / Connaissances des adolescents atteints de maladie inflammatoire chronique intestinale : résultats d'une enquête transversale multicentrique.

AIM: To assess knowledge acquired by adolescents about their inflammatory bowel disease (IBD). METHODS: An anonymous questionnaire was given during consultation to adolescents followed for IBD by pediatricians from 13 hospitals between 1 September 2012 and 1 July 2013. After parental consent, these physicians completed a form at the inclusion of each patient, in which the characteristics of IBD were detailed. The patients mailed back their questionnaire. RESULTS: A total of 124 patients from 12 to 19 years of age were included with a response rate of 82% (all anonymous); 23% of the patients thought that diet was a possible cause of IBD and 22% that one of the targets of their treatment was to cure their disease for good. Of the patients reported having Crohn disease, 46% knew the anoperineal location and 14% knew that Crohn disease can affect the entire digestive tract. Twenty-five percent of the patients were able to name one side effect of azathioprine (88% had already received this treatment), 24% were able to name one side effect of infliximab (54% had already received this treatment), 70% of the adolescents knew that smoking worsens Crohn disease, 68% declared they had learned about their IBD from their pediatrician, and 81% said they would like to receive more information. CONCLUSION: Adolescents with IBD have gaps in their general knowledge and the different treatments of their disease. Their main source of information is their pediatrician, warranting the implementation of customized patient education sessions.

[Congenital portosystemic shunts: experience of the western region of France over 5 years]. / Shunts porto-systémiques congénitaux : expérience du Grand-Ouest sur cinq ans.

INTRODUCTION: Congenital portosystemic shunts (CPS) are rare vascular malformations that lead to liver metabolic modifications. The aim of this study was to describe the management and outcome of CPS in children who were followed in the western region of France and to compare our experience to a literature review. PATIENTS AND METHODS: This retrospective study reports nine children with CPS who were followed in the western region of France between 2008 and 2013. RESULTS: Among these nine children, six were detected by prenatal ultrasonography, one had cholestatic jaundice during the postoperative period, one had cholestatic jaundice during the first days of life, and one had dyspnea and fatigue. Two children had liver tumors. The CPS was intrahepatic for four children and extrahepatic for two children. Three others had a patent ductus venosus. Among the intrahepatic shunts that were discovered before the age of 2 years, three closed spontaneously. The five other shunts were closed surgically or by interventional radiology techniques, after angiography for four children. After closure of eight shunts, the outcome was favorable for six children. Two children presented complications after surgery: portal hypertension and portal thrombus. CONCLUSION: When CPS is suspected, the diagnosis should be confirmed and complications should be investigated. Shunt closure restores portal flow and prevents complications.

[Aquagenic palmoplantar keratoderma in children with cystic fibrosis]. / Kératodermie palmoplantaire aquagénique chez l'enfant mucoviscidosique.

INTRODUCTION: Aquagenic palmoplantar keratoderma (APK) is a cutaneous phenomenon marked by the formation of edematous, translucent papules and plaques on the palms after water immersion. It can be observed in healthy subjects, but while this dermatosis is little known by practitioners treating these patients, most cases of APK have been described in patients with cystic fibrosis (CF). The primary objective of this study was to evaluate the frequency of APK in a population of children with CF. In addition, the relationship between APK and sex, genotype, pancreatic and pulmonary function, body mass index, and sweat chloride levels was analyzed. METHODS: This study was conducted in 60 children, 27 girls and 33 boys, aged 4 months to 18 years, followed at the CF care center at Angers (France) University Hospital, in whom CF had been confirmed by a positive sweat chloride level greater than 60 mmol. APK was determined by questioning searching for modifications of the palms noticed by the patient or his/her family after immersion in water and a clinical examination searching for the same signs before and after immersion of the right hand in a bucket of lukewarm water for 3 minutes (bucket sign). RESULTS: Forty-seven out of 60 children (78%) had a positive bucket sign. Thirty-eight upon these 47 children had already noticed modifications of the skin on their palms, appearing quickly during the bath and 6 had an edema and an increase in skin folds on the palms of the hands even before immersion of their hand in water. No genotype-phenotype correlations were detected in patients with APK, nor were there associations of APK with other phenotypic features of CF. CONCLUSION: APK is very frequent in patients with CF. It is most probably a consequence of the dysfunction of the CFTR protein. It should be systematically sought in all patients with CF. Its discovery in another context should suggest the diagnosis of CF or a carriage to the heterozygous state of a mutation involved in the disease.

[Antineutrophil cytoplasmic autoantibodies in children: clinical features]. / Auto-anticorps anticytoplasme des polynucléaires neutrophiles en pédiatrie : caractéristiques cliniques.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) are usually considered as serological markers of vasculitis (microscopic polyangiitis, granulomatosis with polyangiitis, and Churg-Strauss syndrome), but they have also been described in other diseases. They are rarely observed in children. Therefore, this study aims to describe the clinical spectrum associated with positive ANCA in children. PATIENTS AND METHODS: All the children below 15 years of age, admitted to the Angers University Hospital between June 2004 and June 2010 presenting with an ANCA-positive test by indirect immunofluorescence were included in this study. The exhaustive list of ANCA-positive children was obtained from the immunology unit. Six antigenic targets were routinely tested by Elisa, i.e., proteinase 3, myeloperoxidase, bactericidal permeability increasing protein, cathepsin G, elastase, and lactoferrin. Clinical and biological data were retrospectively collected. RESULTS: Thirty-seven children were identified with positive ANCA in this 6-year period. None of the antigenic targets tested was found in 21 patients. The most frequent diseases associated were inflammatory bowel disease (n=10), infections (n=6), hematological disease (n=5), and juvenile idiopathic arthritis (JIA) (n=4). Patients with JIA presented with a predominance of antielastase antibodies. CONCLUSION: In contrast to the findings usually observed in adults, we obtained a wide spectrum of clinical entities associated with positive ANCA in this cohort. In children, the ANCA test has 2 advantages: to diagnose systemic vasculitis and to differentiate inflammatory bowel disease. Patients with JIA seemed to have more frequent antielastase antibodies: in the future, this finding should be further investigated in larger prospective studies.

[Neonatal diarrhea due to congenital glucose-galactose malabsorption: report of seven cases]. / Diarrhée néonatale par malabsorption du glucose et du galactose : à propos de 7 observations.

Congenital glucose-galactose malabsorption (CGGM) is a rare autosomal recessive disorder, which presents as a protracted diarrhea in early neonatal life. We describe the clinical history, diagnostic evaluation, and management of 7 children with CGGM in western France. There were 4 girls and 3 boys from 5 families, born between 1984 and 2010. The principal complaint was a neonatal onset of watery and acidic severe diarrhea complicated by hypertonic dehydration. The diarrhea stopped with fasting. In 2 cases, the family history supported the diagnosis. In the other cases, elimination of glucose and galactose (lactose) from the diet resulted in the complete resolution of diarrhea symptoms. In 2 cases, the H2 breath tests were positive. In 2 cases, the HGPO or oral glucose tolerance test (OGTT) demonstrated an abnormal curve with glucose and a normal curve with fructose. DNA sequencing was not used. When glucose and galactose were eliminated from the diet, the infants had normal growth and development. In conclusion, CGGM is a rare etiology of neonatal diarrhea; however, the diagnosis is easy to make and the prognosis is excellent.

[Adolescent with anorexia nervosa: consequences on bone mineralization]. / Anorexie mentale de l'adolescent : conséquences sur la minéralisation osseuse.

INTRODUCTION: Anorexia nervosa is responsible for abnormalities in bone mineralization, which are well known and described in adults, but less well documented in adolescents. The aim of this research was to evaluate the frequency and severity and to determine predictive factors for these abnormalities in a population of adolescents with diagnosed anorexia nervosa. PATIENTS AND METHODS: This retrospective study involved 39 female adolescents with anorexia nervosa having undergone dual energy X-ray absorptiometry prior to the age of 18 years. Clinical (age, Tanner puberty stages, weight, body mass index [BMI] at different times during the anorexia phase and amenorrhea features), radiological (bone mineral density [BMD] in Z-score units and in absolute values), and biological (calcemia and vitamin D) parameters were collected. RESULTS: In total, 20 patients (51%) presented osteopenia (Z-score <-1 DS and >-2.5 DS) and 2 (5%) had osteoporosis (Z-score <-2.5 DS). Five (13%) exhibited a Z-score less than -2 DS. BMD expressed in Z-scores correlated with none of the parameters assessed. At univariate analysis, BMD in absolute values correlated with the age at disease onset, BMI, weight loss at the lowest weight achieved and BMI at the time of densitometry (P<0.01). At multivariate analyses, only the correlation with the age at disease onset persisted (P<0.05). CONCLUSION: Bone loss in anorexia nervosa is a complication that may be present as early as adolescence. It must be systematically searched for in all adolescents with severe malnutrition because, even if BMD correlated with nutritional parameters, no clinical predictor for osteoporosis or osteopenia could be identified in this study.

Transient elastography and portal hypertension in pediatric patients with cystic fibrosis Transient elastography and cystic fibrosis.

BACKGROUND: Esophageal varices (EV) are a complication of cystic fibrosis-associated liver disease. Esophagogastroduodenoscopy (EGD) is currently used to diagnose varices but is invasive for pediatric patients. The goal of this study was to explore the relationship between transient elastography (FibroScan®) and the presence of EV in patients with liver disease defined by clinical, laboratory, sonographic, and/or endoscopic criteria. METHODS: 18 patients with cystic fibrosis underwent EGD and transient elastography. 12 patients had EV. RESULTS: Patients with EV had higher FibroScan values than those without varices with median values of 22.4 kPa (14.4-30.4 kPa) vs. 7.9 kPa (4.4-13.7 kPa) (p=0.01). Using a threshold of 12 kPa, four of six patients without EV would not have needed EGD. CONCLUSIONS: Elastography should be recommended for all cystic fibrosis patients with liver disease to follow its progression. A prospective study is needed to define an elastography threshold value that predicts the presence of EV.

[Body composition analysis in patients with cystic fibrosis. Comparison of 3 methods: dual energy x-ray absorptiometry, bioelectrical impedance analysis, and skinfold measurements]. / Composition corporelle des patients mucoviscidosiques - comparaison de 3 techniques de mesure : anthropométrie, absorptiométrie biphotonique et impédancemétrie.

Nutritional status must be closely monitored in cystic fibrosis (CF) patients. This study compared three methods of measuring body composition in CF patients and then examined the relationships between two simple anthropometric markers of nutritional status - tricipital skinfold thickness (TSK) and arm muscular circumference (AMC) - and the results given by each method. Fifty-five patients with CF, 27 females and 28 males, participated in this study. The mean age at the time of the study was 14 ± 5 years, ranging from 4 to 29 years. The four skinfolds (SK) and arm circumference were measured in all patients and fat mass (FM) and AMC were calculated. Fifty patients underwent dual energy x-ray absorptiometry (DEXA) and 38 underwent bioelectrical impedance analysis (BIA). The values for FM as calculated by the three methods were highly correlated, as were the values for lean body mass (LM) (p<0.001). The LM assessed by anthropometry was overestimated by 8 ± 4% compared with DEXA and by 6 ± 7% compared with BIA. BIA overestimated LM by 4 ± 6% compared with DEXA (p<0.001). The LM values measured by SK, DEXA, and BIA were highly correlated with AMC (p<0.001) and FM calculated using these three techniques were highly correlated with TSK (p<0.001). The measurement of TSK and AMC are simple and rapid ways to evaluate body composition. The excellent correlation between the three methods used to measure body composition suggests that they are valid for use in patients with CF, but the results were not identical. The measurement from each technique must be interpreted according to its own norms and comparisons can only be made if the same technique is used in the same patient.

[Transition from pediatric to adult care: experience of a cystic fibrosis care center]. / Passage de l'enfant à l'adulte: l'exemple d'un centre de ressources et de compétences pour la mucoviscidose.

BACKGROUND AND OBJECTIVE: Even though patients with cystic fibrosis (CF) are continuously improving their life expectancy, guidelines for transition to adult services have not been clearly determined yet. The aim of this study was to analyze the management of this transition in the CF care center of Angers, France. PATIENTS AND METHOD: From their medical files, we analyzed the transfer of 22 patients with CF from pediatric to adult care. The perceptions of patients and caregivers regarding this transition were evaluated using anonymous questionnaires. RESULTS: The initial objective was to transfer patients around 18 years of age, offering them 3 or 4 joint consultations with a pediatrician and adult lung specialist. The median age of transfer was 22 years and the median duration of the transition period was 9 months. Half of the patients had only 1 joint transfer consultation during transition. The patient reaching the age of 18 and maturity were the most common criteria mentioned for transfer. All highlighted problems leaving the pediatric team they had grown attached to and its familiar environment. Caregivers described the transfer as a success, whereas half of the patients were dissatisfied with it, with both patients and caregivers indicating that the transition was too short without enough joint consultations. CONCLUSIONS: This study shows that this period is a major life event for the patient with CF. The transition process must be organized with the patient and independent behaviors should be encouraged. Adult and pediatric teams need to cooperate. Based on this experience and former medical data, we suggest a transition program for patients with CF.

[Recommendations for the management of bone demineralization in cystic fibrosis]. / Recommandations pour la prise en charge de la déminéralisation osseuse dans la mucoviscidose.

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

Neonatal screening of cystic fibrosis: diagnostic problems with CFTR mild mutations.

Newborn screening (NBS) of cystic fibrosis (CF) was implemented throughout the whole of France in 2002, but it had been established earlier in three western French regions. It can reveal atypical CF with one or two known CFTR mild mutations, with an uncertain evolution. The sweat test can be normal or borderline. In Brittany, from 1989 to 2004, 196 CF cases were diagnosed (1/2885 births). The incidence of atypical CF diagnosed by NBS is 9.7% (19 from 196). The outcome of 17 (2 lost of view) has been studied, with 9 other atypical CF cases diagnosed by NBS in two other regions. The follow-up period extends from 0.25 to 19.8 years (NBS implemented in Normandy in 1980) with mean age 4.6 years. The most frequent mild mutation is R117H ISV8-7T (50%). At the time of the last visit, nutritional status is normal. All these CF patients are pancreatic sufficient. Only one patient exhibits respiratory infections, whereas 7 others have them intermittently. Two of them had intermittent Pseudomonas aeruginosa colonization at 2.8 and 6.5 years. Mean Shwachman score is 96.7, mean Brasfield score is 22.8. Eight children have had lung function tests (mean follow-up of 10 years): mean FVC was 99% of predicted, mean FEV1 101%, but one of them has FEV1 of 48%. Predicting the phenotype of these atypical CF patients remains difficult, thus complicating any genetic counselling. A regular clinical evaluation is necessary, if possible by a CF unit, because CF symptoms may appear later.

[Quality of training and professional outcomes of medical students in pediatric residency programs: survey of graduating classes between 1990 and 2000, in the western interregion]. / Qualité de la formation et devenir professionnel des étudiants du diplôme d'études spéciales de pédiatrie: enquête auprès des promotions 1990 à 2000 de l'interrégion ouest.

OBJECTIVES: Little information is available to incoming students in pediatrics residency programs on the experiences of past residents. The objective of this study was to investigate the pediatrics training programs and determine the professional outcomes of graduating residents between 1990 and 2000 in the Western Interregion. POPULATION AND METHODS: Questionnaires were distributed to the 187 medical students enrolled in pediatrics residency programs between 1990 and 2000 in the six university hospital centers of the Western Interregion. The questions concerned the details of training, the modes of residency positions, and current professional and personal situations. One hundred and sixty-five (88%) individuals responded. RESULTS: Seventy-seven percent of the practicing pediatricians stated that the training they had received during residency was adapted to their current practice. This percentage was higher for hospital staff physicians (82%) than for the physicians in private practice (50%) or those with salaried positions outside the hospital system (58%). One hundred and twenty-four had either completed post-residency training (97) or were doing so (27) at the time of the survey. All but one were professionally active, three quarters of them in hospitals and, of these, most were in the hospitals where they had trained. Eighty-six percent of the practicing pediatricians said they were satisfied with their professional work and 73% said they were satisfied with their personal lives. CONCLUSION: These results support the current reflection on reforming the residency training program in pediatrics, especially with regard to its prolongation and the diversification of the training options to take into account the individual student's professional orientation.

[Food avoidance emotional disorder in 3 to 10-year-old children: a clinical reality]. / Evitement alimentaire et trouble affectif chez l'enfant.

We underline the clinical importance of a specific eating disorder in 3 to 10 years old children, when the majority of the works about the prepubertal eating disorders focus either on the period just preceding adolescence (often between 10 and 13 years), or on the second half of the first year of the baby. Within the eating disorders described in the literature, we compare the clinical presentation of most of these 3 to 10 years old children with the food avoidance emotional disorder described during adolescence. These problems of eating behaviour (various selective eating with or without provoked vomiting) are ignored for a long time in these young children because of quite a satisfactory growth, but these children are often seen in emergency rooms because of a brutally complete eating refusal. Therapeutic consultations allow these children to express their fears about diseases, poisoning and death, for themselves or for their close relations, in particular the mother, without endangering their body. The early recognition and care of these difficulties of conciliation between the body and the thoughts impose a narrow collaboration between paediatric and psychiatric staffs.

[Antineutrophil cytoplasmic antibodies in cystic fibrosis. Frequency and significance]. / Anticorps anticytoplasme des polynucléaires neutrophiles au cours de la mucoviscidose. Fréquence et signification.

UNLABELLED: Some immune system abnormalities have been reported in cystic fibrosis, particularly the presence of antineutrophil cytoplasmic antibodies (ANCAs). The purpose of this study was to determine the frequency of these antibodies in a population of patients with cystic fibrosis and to assess their relationship with the disease progression. POPULATION AND METHODS: This retrospective study looked for the presence of these antibodies in sera from 64 patients (30 boys and 34 girls) aged one to 29 years. All patients were followed up within the Cystic Fibrosis Center of the University Hospital of Angers. The serum samples were collected in 2001 during the yearly check-up to evaluate disease status. RESULTS: Seven of the 64 patients presented the antibodies. Univariate analysis showed that these patients were significantly older and more often chronically infected with Pseudomonas aeruginosa than the other patients. They also scored significantly more poorly on pulmonary radiography and showed significantly higher IgG and CRP. Multivariate analysis revealed that the two following independent factors were associated with the presence of ANCAs: chronic P. aeruginosa infection and high IgG level. CONCLUSION: This work confirms the abnormally high frequency of antineutrophil cytoplasmic antibodies in patients with cystic fibrosis. These antibodies were observed in the sickest patients with severe infection status. They reflect the impact of inflammatory processes in the pathogenesis of the disease. Detection of these antibodies might be an indication for intensified treatment of bronchial infections.

[Effect of oral biphosphonates in patients with cystic fibrosis and low bone mineral density]. / Efficacité des biphosphonates oraux sur la déminéralisation osseuse des patients atteints de mucoviscidose.

UNLABELLED: Disturbances in bone mineralization are frequent in cystic fibrosis but few studies have focused on the use of biphosphonates in this indication, and none on the use of oral etidronate. We report our experience using this latter treatment. METHODS: The study was retrospective and included five children and three adults with cystic fibrosis (six males and two females) aged seven to 30 years with Z-scores for lumbar bone density lower than -2 SD after one year of calcium (1 g/day) and vitamin D (900 UI/day and 300,000 UI/6 months) supplementation. All were treated during one year with etidronate: four courses of 15 days (one course per trimester) with doses ranging from 4 to 8 mg/kg per day. Calcium and vitamin D supplementation was continued between the etidronate treatment course. Total body and lumbar bone mineral density (BMD) were measured three times: at the beginning and the end of the year of calcium and vitamin D supplementation and at the end of the year of supplementation plus the four courses of etidronate treatment. RESULTS: The increase in BMD in absolute value (g/cm2) and in Z-score was significantly higher (P <0.05) after the year of combined supplementation and etidronate treatment (total body g/cm2: 3+/-1%, Z-score: 2+/-1% and lumbar spine g/cm2: 6+/-5%, Z-score: 3+/-4%) than after supplementation alone (total body g/cm2: -1+/-3%, Z-score: -4+/-3% and lumbar spine g/cm2: -1+/-3%, Z-score: -4+/-4%). Supplementation alone improved the total BMD in only one patient and the lumbar BMD in three, whereas after etidronate treatment the total and lumbar BMD were improved in the eight patients. None of the patients presented with side effects that could be attributed to the treatment. CONCLUSION: Oral etidronate treatment is well-tolerated and capable of improving bone mineralization in patients with cystic fibrosis. Further work will be necessary to determine the optimal dosage and the optimal frequency for the treatment series.

[Benzodiazepine poisoning in a neonate: clinical and toxicokinetic evaluation following enterodialysis with activated charcoal]. / Intoxication par les benzodiazépines chez un nouveau-né: évaluation clinique et toxicocinétique de l'entérodizlyse par le charbon activé.

CASE REPORT: A pregnant woman who was a regular user of anxiolytics was admitted to the maternity ward at 38 weeks and 4 days amenorrhea after a massive overdose of clorazepate dipotassium, a benzodiazepine. The exact quantity ingested was undetermined. The infant, born at 39 weeks, presented no spontaneous breathing and tracheal intubation was necessary in the delivery room. The neonatal blood concentrations of the clorazepate metabolites were very high at delivery (26 mg/l nordiazepam and 3.5 mg/l oxazepam) and showed little change over the next 5 days (16 mg/l nordiazepam and 2.1 mg/l oxazepam, with an apparent half-life of 168 h for nordiazepam and 160 h for oxazepam). By day 6, the infant was still dependent on ventilator support and enterodialysis was begun with repeated doses of activated charcoal (1 g/kg every 6 h by gastric tube). Treatment was continued for 5 days and a spectacular diminution in the serum concentrations of the two metabolites was noted on day 11: 1.5 mg/l nordiazepam and less than 0.1 mg/l oxazepam. The nordiazepam and oxazepam half-lifes were reduced to 42 h and 30 h respectively. The concomitant clinical improvement authorized the weaning from ventilation on day 12. CONCLUSION: This is the first report of the use of enterodialysis to treat severe benzodiazepine poisoning in a neonate. Depuration of the toxin was accelerated and the duration of intensive care was shortened thanks to this technique.

[Mitochondrial cytopathy: an unusual infantile cause of total villous atrophy]. / Cytopathie mitochondriale: une cause inhabituelle d'atrophie villositaire totale chez le nourrisson.

Villous atrophy in an infant immediately suggests food intolerance. We report a case with an unusual cause. This female infant was first examined at 5 months for anorexia and failure to thrive. Intestinal biopsy showed total villous atrophy. A diet excluding gluten and cow milk proteins failed to improve her condition and the infant was hospitalized at 7 months for further investigations. The infant was hypotonic with a head lag. No other clinical sign was noted. Serum transaminases were increased 5- to 10-fold and CSF proteins concentration was increased. Metabolic investigations revealed hyperlactacidaemia and an increased lactate/pyruvate ratio during fasting and feeding, suggesting a mitochondrial cytopathy. Respiratory chain enzymatic activity measurements confirmed the diagnosis and showed severely decreased activities of complexes I, III and IV in both the liver and muscle. Molecular analysis demonstrated depletion of mitochondrial DNA in the liver (75%) and in muscle (97%). The infant was discharged under continuous enteral nutrition. Improvement was of short duration and the infant died at 1 year of age of massive hepatic failure. This is the first report of a mitochondrial DNA depletion with total villous atrophy and malabsorption as early clinical onset. A mitochondrial cytopathy should be considered in such conditions when food exclusion diets fail.