Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome.

International audienceBACKGROUND: Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. RESULTS: Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value

Les patients suivis pour une maladie coeliaque à l'Hôpital d'enfants de Nancy (évolution à long terme (n=29), impact des recommandations successives)

Nous avons évalué à long terme, la croissance et le métabolisme osseux d'enfants suivis à l'Hôpital d'Enfants de Nancy pour maladie coeliaque (MC), et qui ont bénéficié de protocoles thérapeutiques différents. Nous avons inclus ceux dont le suivi était supérieur à 7 ans. Nous avons relevé les paramètres anthropométriques, ostéodensitométriques, les statuts martial et en vitamine D. Vingt neuf patients ont été étudiés, avec un recul de 7,6 à 25,2 ans. Le gluten a été réintroduit chez 25 patients. Quinze ont bénéficié du protocole 3 biopsies avec une tolérance apparente de 60 % (9/15) ; treize patients dont 5 après rechute sous le premier protocole, ont suivi le protocole dit Schmitz , avec une tolérance globale de 69 % (9/13). Sous RSG, on note une amélioration (p<0,05) de la croissance staturo-pondérale, de la corpulence, du poids pour la taille (PIT), de l'hémoglobine (Hb) et du fer sérique. Les paramètres nutritionnels ne s'aggravent pas à 6 et 12 mois de la réintroduction du gluten. Il n'y a pas de différence significative d'évolution des paramètres des patients selon leur régime à la dernière évaluation. Les ostéodensitométires réalisées chez 19 patients montrent un seul patient, sous régime normalisé, dont le z score lombaire est inférieur à -2 DS. Le suivi de ces patients à long terme n'a pas objectivé d'anomalies. Cependant, le RSG doit être repris chez ceux consommant du gluten du fait du risque augmenté de pathologies autoimmunes, de cancers et d'ostéoporose.NANCY1-SCD Medecine (545472101) / SudocSudocFranceF

Contribution à l'étude de la calprotectine fécale dans le suivi des maladies inflammatoires chroniques intestinales (MICI) à début pédiatrique

Après plus de cinquante années de recherches, les MICI de l'enfant restent un mystère pour une part de leur physiopathologie et leur devenir. Les prises en charge sont complexes, parfois inefficaces dans la prévention des rechutes et ce, malgré de récentes innovations thérapeutiques comme les biothérapies. Cette étude pédiatrique originale compare la première poussée de la maladie à la première rémission clinique, chez des enfants naïfs de toute thérapeutique. Elle démontre la variation significative de calprotectine fécale, comparativement à un groupe contrôlé, et sa précession chronologique sur les paramètres inflammatoires et les signes cliniques. La calprotectine fécale, par sa stabilité à l'air ambiant durant 7 jours, est donc un marqueur de choix, reproductible dans l'appréciation de la sévérité d'une poussée clinique, au cours de la rémission, et tout au long de l'évolution de la maladie. La calprotectine fécale est donc un outil indispensable dans le suivi des MICI pédiatriques.NANCY1-SCD Medecine (545472101) / SudocNANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Prise en charge de la diarrhée aigüe du nourrisson en Lorraine

La diarrhée aiguë du nourrisson est une affection courante dans la pratique des médecins généralistes et des pédiatres. Pourtant cette pathologie apparemment bénigne entraîne encore chaque année des décès, même en France. Des recommandations simples existent concernant la prise en charge de la diarrhée du nourrisson. Nous avons donc repris tout d'abord les données actuelles de la littérature à ce sujet, en nous attachant particulièrement au traitement de cette maladie. Puis nous avons réalisé une revue non-exhaustive des différentes études déjà réalisées au sujet de la prise en charge de la diarrhée du nourrisson. Enfin, nous avons enquêté à notre tour et nous livrons ici les résultats de l'étude entreprise en Lorraine après le remboursement des solutions de réhydratation orale. Un audit a été pratiqué auprès des médecins généralistes et des pédiatres de Lorraine et auprès des médecins de la Protection Maternelle et Infantile de Moselle. L'objectif de l'étude était d'évaluer le taux de pesée des nourrissons et le taux de prescription des solutions de réhydratation orale. 51 médecins ont répondu à ce questionnaire, ce qui a permis l'inclusion de 602 nourrissons. Les résultats retrouvés sont conformes à ceux tirés de la littérature. Nous avons alors entrepris une réflexion quant aux pratiques observées, encore trop éloignées des recommandations et nous avons tenté d'envisager des pistes d'amélioration.NANCY1-SCD Medecine (545472101) / SudocNANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Zinc Therapy for Wilson Disease in Children in French Pediatric Centers:

International audienceBackground and Aims: Zinc therapy is considered a good option in Wilson disease (WD), as a first-line treatment in presymptomatic children and a maintenance therapy after the initial chelator therapy. The aim of the study was to determine the practical use of zinc treatment in French pediatric centers. Methods: A national survey was conducted in the 6 French centers using zinc acetate to treat WD. Clinical and biological parameters, dosage, and outcome were recorded. Results: A total of 26 children were reported to be treated with zinc acetate, alone or in association with chelators. Of the 9 children (35%) who received zinc alone as a first-line therapy, 2 were switched to D-penicillamine because of inefficacy and 7 remained on zinc alone, but serum transaminase levels normalized in only 4 of them. Five children (19%) were initially treated with zinc in association with D-penicillamine (n = 4) or Trientine (n = 1) with good efficacy. Among the 12 children (46%) who received zinc as a maintenance therapy after D-penicillamine, no relapse of hepatic cytolysis occurred during a median follow-up of 5.2 years, but 2 of them were switched to Trientine because of zinc-related adverse effects. Epigastric pain was observed in 4 children, and a gastric perforation occurred in 1 child. Conclusions: The present study demonstrates poor efficacy of zinc as first-line therapy to control liver disease in half presymptomatic children and a high incidence of related gastrointestinal adverse effects in children with WD

: L'échinococcose alvéolaire hépatique.

4 pagesInternational audienceHepatic alveolar echinococcosis is a rare parasitic zoonosis, potentially lethal in childhood. It is due to Echinococcosis multilocularis whose larva insidiously develops in the liver. We report the case of a 13-year-old girl, living in the Vosges Mountains, followed for recurrent abdominal pain, with recent worsening. Diagnosis of alveolar echinococcosis was immediately suspected based on the liver ultrasound scan and then confirmed by imaging (CT scan, NMR) and serology. A curative surgical treatment (segmentectomy) was performed 3 months after diagnosis, under oral albendazole treatment, maintained for at least 2 years. Hepatic alveolar echinococcosis usually has a negative prognosis, except if diagnosed early, which allows rapid surgical treatment, as in our patient

Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes

International audienceObjective: To gain insight into the molecular bases of genetically unexplained periodic fever syndromes (PFS) by screening NLRP12, a gene in which only a nonsense and a splice site mutation have so far been identified, and to assess the functional consequences of the identified missense variation.Methods: NLRP12 was screened for mutations by direct sequencing. Functional assays were performed in HEK 293T cells stably expressing the proapoptotic protein ASC and procaspase 1, in order to determine the effects of normal and mutated NLRP12 proteins on speck formation, caspase 1 signaling, and NF-κB activation.Results: A heterozygous NLRP12 missense mutation involving a CpG site (c.1054C>T; p.Arg352Cys) was identified in exon 3, which encodes the nucleotide-binding site (NBS) of the protein, in 2 patients from different countries and carrying different NLRP12 haplotypes. The mutation, which does not alter the inhibitory effect of NLRP12 on NF-κB activation, increases speck formation and activates caspase 1 signaling. To define this new class of PFS, we propose the term NLRP12-associated disorders (NLRP12AD).Conclusion: Given the rarity of known NLRP12-associated disorders, the identification of this NLRP12 molecular defect contributes to the delineation of the clinical spectrum associated with mutations in this gene and highlights the importance of screening NLRP12 in patients presenting with unexplained PFS. This study also demonstrates, by means of functional assays, the deleterious effect of this recurrent missense mutation; the gain of function for speck formation and caspase 1 signaling associated with this NBS mutation is consistent with the inflammatory phenotype of PFS

Efficacy of infliximab in pediatric Crohn's disease: A randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy

Background: Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and "on demand" treatment strategies. Methods: Forty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 ± 2.2 years) with a severe flare-up (Harvey-Bradshaw Index [HBI] ≥ 5, erythrocyte sedimentation rate [ESR] > 20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/ W6. At W10, clinical remission (HBI < 5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, "on demand" on relapse. Results: In all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 ± 2.5 (WO) vs. 1.1 ± 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial. Conclusions: IFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an "on demand" basis. Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease.

Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3-17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8-7.3) of infliximab during a median time period of 4 months (1-17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey-Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment