[An infant with prolonged jaundice]. / Een zuigeling met persisterende icterus.

BACKGROUND: In every neonate presenting with prolonged jaundice persisting beyond day 21 of life, neonatal cholestasis should always be excluded even if the infant is breast fed. Pale stools are an alarm symptom and additional tests for neonatal cholestasis should be carried out directly. CASE DESCRIPTION: We describe the case of a five-week-old girl of Chilean origin who was referred with conjugated hyperbilirubinaemia. The jaundice had possibly arisen directly after birth, but due to the dark skin colour of the neonate the jaundice was not recognized as such, although her scleras were yellow. According to the stool colour card, her stools were pale. The findings of a histological examination of a liver biopsy confirmed the diagnosis of biliary atresia, for which a Kasai hepatoportoenterostomy was performed. CONCLUSION: Neonatal cholestasis is always pathological and requires further investigation. In infants with dark skin, jaundice is sometimes difficult to see and inspection of the scleras should give the definitive answer.

Outcome of initially nonoperative treatment for acute simple appendicitis in children.

PURPOSE: To compare the outcome of initially nonoperative treatment with immediate appendectomy for simple appendicitis in children. METHODS: Between September 2012 and June 2014 children aged 7-17 years with a radiologically confirmed simple appendicitis were invited to participate in a multicentre prospective cohort study in which they were treated with an initially nonoperative treatment strategy; nonparticipants underwent immediate appendectomy. In October 2015, their rates of complications and subsequent appendectomies, and health-related quality of life (HRQOL) were assessed. RESULTS: In this period, 25 children were treated with an initially nonoperative treatment strategy and 19 with immediate appendectomy; median (range) follow-up was 25 (16-36) and 26 (17-34) months, respectively. The percentage [95%CI] of patients experiencing complications in the initially nonoperative group and the immediate appendectomy group was 12 [4-30]% and 11 [3-31]%, respectively. In total 6/25 children (24%) underwent an appendectomy; none of the 6 patients operated subsequently experienced any postappendectomy complications. Overall, HRQOL in the nonoperative treatment group was similar to that of healthy peers. CONCLUSIONS: Outcome of initially nonoperative treatment for acute simple appendicitis in children is similar to the outcome in those who undergo immediate appendectomy. Initially nonoperative management seems to be able to avoid appendectomy in 3 out of 4 children. LEVEL OF EVIDENCE: 2 (prospective comparative study). This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Initial antibiotic treatment for acute simple appendicitis in children is safe: Short-term results from a multicenter, prospective cohort study.

BACKGROUND: Initial antibiotic treatment for acute appendicitis has been shown to be safe in adults; so far, not much is known about the safety and efficacy of this treatment in children. The aims of this study were to investigate the feasibility of a randomized controlled trial (RCT) evaluating initial antibiotic treatment for acute appendectomy in children with acute simple appendicitis and to evaluate the safety of this approach. METHODS: In a multicenter, prospective cohort study patients aged 7-17 years with a radiologically confirmed simple appendicitis were eligible. Intravenous antibiotics (amoxicillin/clavulanic acid 250/25 mg/kg 4 times daily; maximum 6,000/600 mg/d and gentamicin 7 mg/kg once daily) were administered for 48-72 hours. Clinical reevaluation every 6 hours, daily blood samples, and ultrasound follow-up after 48 hours was performed. In case of improvement after 48 hours, oral antibiotics were given for a total of 7 days. At any time, in case of clinical deterioration or non-improvement after 72 hours, an appendectomy could be performed. Follow-up continued until 8 weeks after discharge. Adverse events were defined as major complications of antibiotic treatment, such as allergic reactions, perforated appendicitis, and recurrent appendicitis. RESULTS: Of 44 eligible patients, 25 participated (inclusion rate, 57%; 95% CI, 42%-70%). Delayed appendectomy was performed in 2, and the other 23 were without symptoms at the 8 weeks follow-up. Minor complications occurred in three patients. None of the patients suffered from an adverse event or a recurrent appendicitis. CONCLUSION: Our study shows that an RCT comparing initial antibiotic treatment strategy with urgent appendectomy is feasible in children; the intervention seems to be safe.

Occult constipation: faecal retention as a cause of recurrent abdominal pain in children.

UNLABELLED: Recurrent abdominal pain (RAP) in children is generally believed to be functional. In practice, many children with RAP become pain-free with laxative therapy. The aims of the study were to establish the role of (occult) constipation in RAP and to investigate whether patients diagnosed with (occult) constipation could be identified by history and physical examination. During 2 years, all patients (age 4-16 years, secondary referral) fulfilling Apley criteria of RAP were included. After exclusion of gastrointestinal infections and food intolerance, laxatives were advised when pain persisted. (Occult) constipation was defined as 'abdominal pain disappearing with laxative treatment and not reappearing within a 6 month follow up period'; 'occult constipation' was diagnosed in patients who did not fulfil the Rome criteria of constipation. Two hundred children (87 M; median age 8.8 years) were evaluated. (Occult) constipation was found in 92 patients (46 %). Of these, 18 had considerable relief of pain when treated for a somatic cause but experienced complete relief only after laxative measures; they were considered to have two diagnoses. Using multivariate analysis, a simple model was developed with cystitis in past history, early satiety and flatulence as predictors for (occult) constipation. The risk of (occult) constipation ranged from 18/58 if no predictor was present to 4/4 if all three were present. CONCLUSION: Laxatives played a pivotal role in the recovery of patients with RAP. We developed a simple model to identify patients at risk of having (occult) constipation.

Composition and diversity of the duodenal mucosa-associated microbiome in children with untreated coeliac disease.

BACKGROUND: Intestinal microbiome may play a role in the pathogenesis of coeliac disease (CD). Studies comparing intestinal microbiome in children with and without CD are contradictory. AIM: To compare the composition and diversity of the duodenal mucosa-associated microbiome in children with untreated CD and control children without CD and to identify specific gut bacteria associated with CD at diagnosis. METHODS: Total microbiome profile in small bowel biopsies of 42 children (21 with untreated CD and 21 age-matched controls) were analyzed by means of IS-pro, a 16S-23S interspacer (IS) region-based profiling method. RESULTS: Both groups showed a similar mucosa-associated microbiome pattern and diversity, with high concentrations of the genera Streptococcus, Lactobacillus, and Clostridium. CONCLUSION: Mucosa-associated duodenal microbiome composition and diversity did not differ between children with untreated CD and control children. Duodenal mucosa-associated bacteria do not seem to play an important role in the pathogenesis of CD.

[A girl with an itchy skin disease]. / Een meisje met een jeukende huidaandoening.

A 10-year-old girl presented with chronic, itchy papulo-vesiculous skin lesions. Diagnosis of dermatitis herpetiformis was established based on elevated IgA endomysium and transglutaminase type 2 antibodies, and histological findings on skin biopsy. Dermatitis herpetiformis is the cutaneous expression of celiac disease. Treatment consists of gluten-free diet and diafenylsulfon.

[Double-balloon enteroscopy in children: indications, safety, and efficacy]. / Dubbelballonenteroscopie bij kinderen: indicaties, veiligheid en effectiviteit.

BACKGROUND: Double-balloon enteroscopy is a technique that utilises an endoscope equipped with an overtube to inspect the entire small bowel. Diagnostic and therapeutic procedures can be performed during this type of endoscopy. So far, the use of this technique in children has been limited. In this article, we present a case illustrating the indication, efficacy and safety of this technique in the paediatric setting. CASE DESCRIPTION: In a 17-year-old girl with chronic abdominal pain and iron deficiency anaemia, neither gastroduodenoscopy nor ileocolonoscopy revealed any abnormality. Video capsule endoscopy revealed a few suspicious erosive lesions and ulcerations, presumed to be located in the ileum. A double-balloon enteroscopy was then performed during which an ulcer was seen on a small-bowel stenosis; this was consistent with the diagnosis of Crohn's disease. The symptoms diminished after treatment with budesonide and azathioprine was initiated. CONCLUSION: Double-balloon enteroscopy also appears to be an effective and safe method of diagnosing and performing therapeutic interventions in paediatric small bowel pathology.

Eosinophilic esophagitis after esophageal atresia: is there an association? Case presentation and literature review.

Eosinophilic esophagitis (EoE) is a relatively new condition resulting in dysphagia or symptoms resembling gastroesophageal reflux disease, symptoms that also are common in patients with a history of esophageal atresia. We present 2 patients with persistent dysphagia after repair of esophageal atresia that was caused by EoE. Although the exact etiology and pathogenesis of EoE remain unclear, it is now generally accepted that it is the result of a T-helper cell 2-type immune response with a crucial role for the eosinophil-specific chemotaxis factor eotaxin 3 and eosinophils. Because there are genetic similarities between esophageal atresia and EoE, we speculate that patients with esophageal atresia are at increased risk for developing EoE.

Clinical practice : coeliac disease.

UNLABELLED: Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100-200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. CONCLUSION: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted.

Empty colon: a pitfall in the assessment of colonic transit time.

We report a misleading outcome of colonic transit time (CTT) assessment in an adolescent girl with functional constipation. We found prolonged total and right segmental CTT despite high doses of oral polyethylene glycol 4000 and repeated treatment with polyethylene glycol-electrolyte solution (Klean-Prep®) by nasogastric tube. A colonoscopy aiming at disimpaction of a possible faecal mass revealed an empty colon with dozens of radio-opaque markers adhered to the colonic wall. This report shows that the result of a CTT cannot be accepted blindly. Especially the clustering of many markers within narrow margins might point at entrapment of markers in mucus against the colonic wall.

[There is something coming out of the anus of my child]. / Er komt bij mijn kind iets uit de anus.

The diagnosis of anal protrusions in children may be difficult, because the protrusion often occurs only after defaecation, and is usually invisible during the consultation. We present three cases of children with rectal prolapse (4-year-old boy), polyp (4-year-old boy), and external haemorrhoids (3-year-old boy), respectively. In each case, the diagnosis could be made after parents had sent a picture of the phenomenon. The first patient recovered after laxative therapy, the second after polypectomy, and in the third patient, the haemorrhoid persisted, despite laxative therapy and physiotherapy.

[Guideline 'Coeliac disease and dermatitis herpetiformis']. / Richtlijn 'Coeliakie en dermatitis herpetiformis'.

The Dutch evidence-based guideline 'Coeliac disease and dermatitis herpetiformis' contains instructions for detection and treatment of coeliac disease. Coeliac disease has a high prevalence: 0.5 - 1.3%. The disease has a broad spectrum of symptoms, frequently also outside the gastrointestinal tract. Relatives of patients and persons with autoimmune diseases, microscopic colitis, IgA deficiency and syndromes of Down, Turner and Williams have an increased risk of coeliac disease. Detection is carried out by determination of IgA antibodies to tissue transglutaminase and endomysium. Testing for IgA antibodies to gliadin is only recommended in children younger than 2 years. Absence of HLA-DQ2 and DQ8 indicates that coeliac disease is most unlikely. The diagnosis should be confirmed by small bowel biopsy. Single biopsy following gluten ingestion is sufficient for diagnosis at all ages. After the diagnosis, patients should be referred to a dietician. Additionally, a yearly follow-up by a paediatrician or internal medical specialist with appropriate gastroenterology specialisation is recommended.

[A premature neonate with a big belly]. / Een prematuur met een bolle buik.

A premature neonate, presenting with vomiting, abdominal distention and rectal blood loss, was found to have pneumatosis intestinalis on plain abdominal X-ray. These findings are indicative of necrotizing enterocolitis.

Clinical practice: Breastfeeding and the prevention of allergy.

The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fueled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4-6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations.

Is gluten challenge really necessary for the diagnosis of coeliac disease in children younger than age 2 years?

OBJECTIVE: In the diagnosis of coeliac disease (CD), gluten challenge is recommended for children under the age of 2 years at initial biopsy. The aim of the study was to investigate the diagnostic yield of gluten challenge in this group of children. PATIENTS AND METHODS: We included children aged 2 years or younger who were analysed for possible CD and who had villous atrophy at initial small bowel biopsy in the period 1993-2004. We subsequently identified all patients who underwent a complete gluten challenge. RESULTS: We identified 333 children with possible CD. In 100 children (30%), a gluten challenge was performed, with the diagnosis being confirmed in 97. Retrospectively, in 2 of the 3 children without mucosal relapse, data available before gluten challenge did not justify the initial diagnosis of CD. In the third patient, transient gluten intolerance could not be excluded. At first biopsy, the 2 children without mucosal relapse had negative serological parameters, whereas the third patient had IgA antigliadin antibodies, but no IgA anti-endomysium antibodies (EMA). Indeed, all of the patients with EMA at diagnosis had a relapse at gluten challenge. CONCLUSIONS: Routine gluten challenge in children younger than 2 years at initial diagnosis of CD has an extremely low diagnostic yield. We suggest that routine gluten challenge in this group of patients is not necessary when patients have villous atrophy in combination with EMA. Therefore, a revision of the current diagnostic criteria has to be considered.

Infliximab dependency in pediatric Crohn's disease: long-term follow-up of an unselected cohort.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD patients initially responding to infliximab therapy. METHODS: All pediatric patients treated with infliximab by pediatric gastroenterologists in the Netherlands because of severe luminal or fistulizing CD with initial response to infliximab therapy were reviewed. Duration of therapy, clinical response and adverse events were recorded. RESULTS: Sixty-six CD patients (37 boys) in 10 hospitals were initially responding to infliximab therapy. Mean age at the start of infliximab therapy was 14.5 years (range, 8.1-18.5 years). Mean follow-up since infliximab was started was 41.3 months (range 12-165). In total, 991 infusions were administered. Analysis demonstrates that 15.2% of patients had prolonged response, while 56.1% were infliximab dependent and 28.8% lost response. In total, 10 patients (15.2%) developed an infection during infliximab therapy and 8 (12.1%) had an immediate allergic reaction. CONCLUSIONS: Good clinical response to maintenance infliximab therapy was seen in 70% of patients. Infliximab maintenance therapy seems very effective and safe in pediatric CD. However, more than half of the patients in this cohort is dependent on repeated infliximab infusions. The number of infliximab infusions received when patients lost response to infliximab was diverse. There was no statistical difference regarding response to infliximab therapy when started early as compared to later in the course of Crohn's disease.

Esophagitis and Barrett esophagus after correction of esophageal atresia.

BACKGROUND: Gastroesophageal reflux is a frequent problem after esophageal atresia (EA) repair. Our aim was to determine the prevalence of esophagitis and Barrett esophagus more than 10 years after repair of EA. METHODS: Ninety-two patients treated between 1973 and 1985 were included in this prospective study. A questionnaire was completed by 86 patients; esophagogastroscopy was performed in 49 patients. RESULTS: Only 36 patients had no complaints at all. Thirty-one patients complained of difficulties swallowing solid food; 23 complained of heartburn. Esophagogastroscopy revealed grade 3 esophagitis in 2 patients and a macroscopic image of Barrett esophagus in 2. Histology showed esophagitis in 30 patients, gastric metaplasia in 3, and no intestinal metaplasia (Barrett esophagus). CONCLUSIONS: For epidemiologic reasons, that is, the short interval of follow-up (10 years) and the low compliance of the study group, larger numbers are needed to decide if routine long-term endoscopic screening after repair of EA is necessary. For now, it cannot yet be recommended. The prevalence of symptoms of gastroesophageal reflux disease in this study group is higher than that in the general population, but we found no severe complications of gastroesophageal reflux in the pediatric age group.