Management of Peutz-Jeghers Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group.

Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps, and characteristic mucocutaneous freckling. Development of small bowel intestinal polyps may lead to intussusception in children may require emergency laparotomy with potential loss of bowel. Gastrointestinal polyps may lead to bleeding and anemia. This European Society for Paediatric Gastroenterology Hepatology and Nutrition position paper provides a guide for diagnosis, assessment, and management of PJS in children and adolescents and guidance on avoiding complications from PJS or from the endoscopic procedures performed on these patients.This is the first position paper regarding PJS published by European Society for Paediatric Gastroenterology Hepatology and Nutrition. Literature from PubMed, Medline, and Embase was reviewed and in the absence of evidence, recommendations reflect the opinion of pediatric and adult experts involved in the care of polyposis syndromes. Because many of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, some of the recommendations are based on expert opinion. This position paper will be helpful in the appropriate management and timing of procedures in children and adolescents with PJS.

Clinical and manometric characteristics of Allgrove syndrome.

OBJECTIVE: The association of adrenocorticotropic hormone (ACTH) insensitivity with achalasia and alacrimia (Allgrove syndrome, 3A) constitutes a rare multisystem disorder. Its evolution is not well known. The aim of this study was to describe clinical and esophageal manometric characteristics and outcomes in Allgrove syndrome. PATIENTS AND METHODS: This multicenter retrospective study compared clinical and manometric characteristics at diagnosis and on follow-up of 9 children presenting with 3A (mean age at diagnosis 7.1 years) with those of 9 children with idiopathic achalasia (IA) (mean age at diagnosis 8.3 years). RESULTS: At the time of diagnosis, 3 children with 3A presented with no digestive or respiratory signs because they were identified during a family screening; 1 remained asymptomatic 8 years later. ACTH levels were high in patients with 3A. All of the patients with IA were symptomatic at diagnosis. No significant difference was observed when comparing any of the manometric parameters of the first esophageal manometry of 3A with those of IA. Seven children with 3A were operated on using the Heller procedure, completed by pneumatic esophageal dilation in 2 of these 7. One patient with 3A was treated only by nifedipine. Failure of treatment was observed in 3 children with 3A and 1 child with IA, partial success in 4 with 3A and 1 with IA, and total success in 2 with 3A and 7 with IA (P < 0.03). Control manometry showed that in the 3A group, partial success after surgery was always associated with abnormally low or normal lower esophageal sphincter (LES) pressure, whereas failure after surgery was associated with high LES pressure. CONCLUSIONS: Our data showed that 3A presented a more severe course than IA despite presymptomatic diagnosis in cases of family screening. The high LES pressure noted in some patients with 3A is suggestive of a peculiar pattern in 3A affecting the LES and the lower part of the esophagus.

Evaluation of guidelines for management of familial adenomatous polyposis in a multicenter pediatric cohort.

OBJECTIVE: To retrospectively assess, in a pediatric multicenter cohort, guidelines for the management of familial adenomatous polyposis (FAP). METHODS: Ten centers from the French-speaking Pediatric Gastroenterology Hepatology and Nutrition Group provided follow-up data on patients up to 18 years of age. Clinical records, genetic test results, endoscopy with histopathology examination, and therapeutic modalities were reviewed. RESULTS: A total of 70 children from 47 families were included. When initial consultation resulted from a surveillance program because of an affected family member, 12 of 59 children were already symptomatic. Among 11 patients whose initial consultation was based only on symptoms, families were unaware at the time of a familial FAP history for 7 children, whereas only 4 cases were sporadic. A panel of 27 different pathogenic adenomatous polyposis coli (APC) germ-line mutations and large genomic deletions were identified in 43 families. Extracolonic manifestations were found in half of the patients. As part of the standard practice for initial screening, the entire cohort underwent colonoscopy, which revealed adenoma above an intact rectosigmoid in 8 cases. Prophylactic colectomy was performed in 42 cases; high-grade dysplastic adenoma and 1 invasive carcinoma were detected in 6 children. For timing of surgery, indications were in accordance with recent international guidelines. CONCLUSIONS: Defining optimal screening and therapeutic modalities in pediatric FAP cohorts is a challenge. Specific advice for genetic screening, endoscopy surveillance, and type of surgery based on recent guidelines is recommended.

Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children.

AIMS: The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori (H pylori) eradication rates in children and to assess the effect of antimicrobial susceptibility. PATIENTS AND METHODS: Prospective, open-label, multicenter study. Children received randomly either a 10-day sequential treatment comprising omeprazole (OME) with amoxicillin for 5 days and OME, clarithromycin (CLA), and metronidazole (MET) for the remaining 5 days, or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain. H pylori eradication was assessed by C-urea breath test. RESULTS: One hundred sixty-five children, 95 girls and 70 boys, of median age 10.4 years, were included. The intention-to-treat (ITT) eradication rate was 76.9% (sequential 68/83 = 81.9%, triple therapy 59/82 = 71.9%, ns), and the per-protocol (PP) eradication rate was 84.6% (sequential 68/77 = 88.3%, triple therapy 59/73 = 81.8%, ns). Eradication rates tended to be higher using the sequential treatment, but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains (87.8% vs 68.5%, odds ratio [OR] 3.3, P = 0.03). Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains (ITT: 56.2% vs 72.7%, OR 5.5, P = 0.008; PP 64.3% vs 80.0%, OR 7.9, P = 0.009). Both treatments were well tolerated. CONCLUSIONS: Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains. Sequential treatment can be used as a first-line therapy, but only in areas with a low CLA resistance rate.

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] > or =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.

Atypical Rothmund-Thomson syndrome in a patient with compound heterozygous mutations in RECQL4 gene and phenotypic features in RECQL4 syndromes.

We describe the natural history of the RTSII phenotype in a 7-year-old boy who developed intrauterine and postnatal growth retardation, failure to thrive and persisting diarrhoea. The growth hormone stimulation test identified an isolated growth hormone deficiency. Since infancy, the patient manifested skin lesions characterized by a very mild poikilodermic-like appearance on the cheeks only, widespread café-au-lait spots and the absence of eyebrows and eyelashes. There was no cataract. Orthopaedic and radiologic work-up identified the absence of thumb anomaly and radial head luxation and patellar hypoplasia. Neurologic, cognitive milestones and intelligence were normal. The cytogenetic work-up did not show any anomaly. Based on this clinical presentation, we carried out a sequencing analysis of the RECQL4 gene, which is responsible for Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes and found a splice site mutation (IVS10-1G>A) and a nucleotide substitution in exon 12 (L638P). The mother was identified as a carrier for the substitution in exon 12 and the father for the splice site mutation, respectively. An analysis of the transcripts focused on the RECQL4 helicase domain: in the proband only those generated from the maternal L638 allele were present. This case report emphasizes the clinical overlap between RAPADILINO and Rothmund-Thomson syndromes within a continuum phenotypic spectrum. The distinctive set of clinical signs displayed by the patient may be accounted for by his unique combination of two different RECQL4 mutations. The molecular findings provide information that enhances our comprehension of genotype-phenotype correlations in RECQL4 diseases, enables a more precise genetic counseling to the parents and facilitates a more appropriate long-term follow-up to the affected child.

Capsule endoscopy in paediatrics: multicentric Belgian study.

BACKGROUND AND STUDY AIMS: Capsule Endoscopy (CE) is a noninvasive procedure for evaluating small bowel disease. Data concerning children are scarce. The aim of the present report was to review all paediatric cases investigated by CE in Belgium. PATIENTS AND METHODS: The seven Belgian academic hospitals using the CE device (Given) were asked to collect information on CE performed in patients < or = 18 years. Main indications for performing VCE, former radiological and endoscopic procedures were collected, as well as final diagnosis and clinical impact of VCE findings. RESULTS: From November 2002 until December 2005, VCE was performed in 17 children (mean age : 11.9 years, range : 5-18). Indications were occult gastro-intestinal bleeding (OGIB) and/or iron deficiency anaemia (IDA) (10 cases) and chronic and/or recurrent abdominal pain (7 cases). Mean duration of symptoms was 8.6 months. The mean number of endoscopic and radiological procedures before performing CE was 4.2 per patient. Detected lesions were ulcerations (6 cases), jejunal varices (1), ileo-ileal invagination (2), active bleeding (1), and normal findings (7). In the indication of OGIB/IDA, relevant findings having an impact on the diagnosis were found in 60% of the cases. In the group with chronic and recurrent abdominal pain, CE brought relevant findings in 43%. CE findings had an impact on therapy in 44% of the patients. CONCLUSIONS: CE could be a useful tool for clinical work-up of difficult paediatric cases, not only in the indication of IDA/OGIB, but also for selected cases of recurrent abdominal pain, but prospective controlled trials including emerging techniques like CT enterography are mandatory.

[Helicobacter pylori infection and eradication are not related to glycosylated hemoglobin levels (HbA1c) in young patients with type 1 diabetes]. / L'infection par Helicobacter pylori et son éradication ne sont pas liées aux taux d'hémoglobine glyquée des jeunes diabétiques de type 1.

OBJECTIVE: Helicobacter pylori (Hp) is a chronic stomach infection common throughout the world. The pediatric diabetes literature on the relation between Hp and HbA1c is sparse and controversial. This study aimed to investigate this relation. METHODS: The study included 100 youth with type 1 diabetes and seropositive for Hp (European Caucasians: n=49; Moghrabin Caucasians: n=51). Mean socioeconomic status was lower among the latter. Hp infection was demonstrated by the (13)C-urea breath test and a gastric biopsy for antibiotic susceptibility testing. HbA1c levels were measured for a year (mean: 6 measurements; upper normal limit: 6.2%) before and after Hp eradication, which was proved by the (13)C-urea breath test. RESULTS: Of 100 Hp-seropositive patients, 49 had active Hp infections and were treated. Mean age+/-SD was 14.2+/-2.8 years, and duration of diabetes at Hp diagnosis was 6.2 +/-2.3 years. Hp infection was eradicated in 38/49 subjects (78%). Eleven (22%) remained infected and required a second treatment. The two subgroups did not differ for age, duration of diabetes or pretreatment HbA1c levels (7.3+/-1.5% versus 7.8+/-0.8%; p=0.16). Mean HbA1c levels in the 49 infected subjects did not differ significantly in the year before and after eradication (7.4+/-1.3% versus 7.9+/-1.1%; p=0.08). Prevalence of infection was higher among youth of North African than European ancestry (47% versus 22%; p<0.001). Their HbA1c levels, however, did not differ (7.3+/-1.5% versus 7.7+/-0.9%; p=0.31), nor did age or duration of diabetes. Among the 100 Hp-seropositive patients, vague abdominal pain was reported by 45 of them; only 24 had active Hp infections. CONCLUSION: Before treatment, patients seropositive for Hp did not differ in HbA1c levels or abdominal complaints according to whether they had active Hp infection. Hp infection was twice as frequent in Moghrabin Caucasians than in European Caucasians, perhaps associated with their lower socioeconomic status. HbA1c levels were similar in patients with and without Hp eradication after one treatment. After a one-year follow-up, Hp eradication had no significant effect on HbA1c levels.

Opsoclonus-myoclonus associated with celiac disease.

Celiac disease may be associated with various neurologic manifestations, most commonly cerebellar ataxia. This report describes a 2-year-old male who presented with opsoclonus-myoclonus syndrome including action myoclonus, palpebral flutter, opsoclonus, and ataxia. Given the severity of ataxia, the child was unable to sit or walk independently. Brain magnetic resonance imaging was normal on two occasions (4-week interval). Oligoclonal bands were found in the cerebrospinal fluid. Blood and serum examinations were unremarkable, with no evidence of infectious seroconversion. However autoantibody testing indicated the presence of antigliadin antibodies of immunoglobulin A subtype, anti-endomysial antibodies, and anti-CV2 antibodies that were not, however, detected in the cerebrospinal fluid. Duodenal biopsy documented villous atrophy confirming the diagnosis of celiac disease. This case confirms that initial presentation of celiac disease may be restricted to neurologic features. We suggest that a search for evidence for celiac disease should be included in the evaluation of opsoclonus-myoclonus.

Food allergy and constipation in childhood: how functional is it?

An increasing incidence of food allergy, especially to cow's milk proteins, is observed in children living in the industrialized regions of the world. In some cases responding to an eviction diet excluding offending foods, the 'functional' constipation can be caused by inflammation of the intestinal wall infiltrated by eosinophils. Understanding the complex mechanisms involved could help to improve the management of idiopathic functional constipation in children by addressing the aetiology instead of treating the symptoms.