Vitamine B12 deficiency in children: a diagnostic challenge.

Cobalamin or vitamin B12 (vitB12) is involved in DNA synthesis, haematopoiesis and myelinisation. Consequently, vitB12 deficiency causes various symptoms, such as megaloblastic anaemia, neurologic signs or pancytopenia. Despite possible severe symptoms, vitB12 deficiency can present asymptomatically. We report six paediatric patients with different aetiologies of vitB12 deficiency ranging from a subtle to a more overt presentation. VitB12 deficiency is a diagnostic challenge due to the lack of consensus on normal values of vitB12 and its co-markers (folate, holotranscobalamin, methylmalonic acid, homocysteine) and the lack in specificity and sensitivity of the serum vitB12 analysis. All cases were treated with parenteral vitB12. Last decades, evidence supporting high dose oral treatment being as effective as the intramuscular (IM) therapy, also in children, is growing.

Not all pediatric intestinal polyps are alike.

BACKGROUND/AIMS: In childhood, clinical presentation of intes- tinal polyps is variable. Painless rectal red blood loss is the most common presenting sign. Most polyps are sporadic, isolated and benign. However, it is important to correctly identify exceptions. Rare inherited polyposis syndromes need to be recognized because of their increased risk of intestinal and extra-intestinal malignancies. Furthermore, a correct diagnosis and treatment of rare gastro-intestinal malignancies is crucial. METHODS: Between 2016 and 2018 we encountered 4 different types of intestinal polyps. A database search was performed and patient files were checked for clinical manifestations and histo- pathology. Literature was searched to recapitulate red flags for these syndromes, probability of underlying genetic disorders and diagnostic criteria. RESULTS: Between 2016 and 2018, 28 patients presented at the Ghent University Hospital with 30 juvenile polyps. Furthermore, we diagnosed juvenile polyposis syndrome, Li Fraumeni syndrome and familial adenomatous polyposis (FAP) in 1 patient each, whilst 2 FAP patients were in follow-up. Each of these diagnoses has a different lifetime risk of (extra)-intestinal malignancy and requires a different approach and follow-up. Histopathology and genetic testing play an important role in identifying these syndromes in pediatric patients. CONCLUSION: Although most intestinal polyps in childhood are benign juvenile polyps that require no follow-up, rare inherited syndromes should be considered and correctly diagnosed since adequate follow-up is necessary to reduce morbidity and mortality from both gastrointestinal and extraintestinal complications and malignancies.

Acid-base disturbances in dehydrated patients with cystic fibrosis : four case reports with review of literature.

Most episodes of vomiting, reduced intake and diarrhoea in children can be evaluated and treated without additional tests. However, when the degree of clinical dehydration is not in line with the patient's medical history, other diagnoses should be suspected. In the presence of a hyponatraemic hypochloraemic metabolic alkalosis, cystic fibrosis (CF) should be included in the differential diagnosis, especially if there is failure to thrive even in the absence of respiratory symptoms. Furthermore, young patients diagnosed with CF have a higher risk for an acute electrolyte decompensation caused by increased salt and fluid losses. We present 4 paediatric cases to raise the awareness of electrolyte disturbances in CF patients.

The long-term effect and adherence of a low fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) diet in patients with irritable bowel syndrome.

BACKGROUND: Short-term trials with a low-FODMAP (fermentable oligosaccharides disaccharides monosaccharides and polyols) diet (LFD) show promising results in the symptomatic management of irritable bowel syndrome (IBS). The present study investigated the long-term adherence to an LFD diet, factors associated with adherence, and associations between LFD and quality of life (QOL), IBS symptoms and disease course on a long-term basis. METHODS: A retrospective cross-sectional study was conducted. Two hundred and thirty-four patients were enrolled from Ghent University hospital. Health-related QOL, long-term adherence to the LFD, disease course and IBS symptoms were assessed using a validated and self-developed questionnaire. RESULTS: Ninety (38.5%) patients completed the questionnaires. The median time span between the first dietary consultation and completion of the questionnaires was 99.5 weeks (approaching 2 years). The predominant disease course was mild IBS with an indolent course (43.0%). Eighty percent reported still following a diet in which certain FODMAP-rich food types are avoided. Eighty patients (88.9%) were satisfied that they follow or had followed the diet. The IBS-QOL did not differ between patients following the diet strictly and patients deviating from the diet (P = 0.669). Patients still following the LFD experienced less severe abdominal pain than patients who stopped following the diet (P = 0.044). CONCLUSIONS: The long-term adherence and satisfaction with the LFD is high in patients with IBS. Nevertheless, patients indicated that it was difficult to follow the LFD in daily life. Practical issues, social factors and the absence of symptoms were indicated as the main reasons for a drop in adherence.

Hepatitis B virus vaccination and revaccination response in children diagnosed with coeliac disease : a multicentre prospective study.

AIM: This study evaluates hepatitis B virus (HBV) vaccination response in children with celiac disease (CD). Response in initial non-responders after a single booster vaccination as well as factors influencing HBV vaccination response were evaluated. METHODOLOGY: Anti-hepatitis B surface antibodies (a-HBsAB) were checked in all children with CD and a documented complete HBV vaccination. An a-HBsAB <10 U/L was considered as non-response. A single intramuscular HBV-vaccine booster was advised to all non-responders. Response was checked at the next appointment. RESULTS: 133 children with CD were included, median age of 7.3 years (range 1.7-17.3) and 46 (35%) were male. The age at CD diagnosis was 6.0 years (range 1.1-15.7). HBV non-response was documented in 55% (n=73/133). No other factors were influencing the response. A booster was documented in 34/73 (47 %) initial non-responders (3 refused (4%), 36 (49%) had no follow up). Response after booster vaccination resulted in immunity in 22/34 (65%) and persisting non-response in 12/34 (35%). A single booster is able to reduce non-response from 55% (73/133) to 23% (22/94). CONCLUSION: A significantly lower immune response following HBV vaccination in children with CD was confirmed. A single intramuscular booster vaccination is able to induce a serologic response in two thirds of the initial non-responders. Control of HBV vaccination response has to become part of the follow-up in CD patients.

Rectal red blood loss in a healthy toddler is not always a juvenile polyp.

Aim Heterotopic gastric mucosa is a well-known congenital anomaly in Meckel's diverticula and duplication cysts. Solitary heterotopic gastric mucosa in the rectum is a rare and frequently overlooked abnormality. Starting from a patient history, the literature is searched and all cases reported over the past 20 years are reviewed and compared to a summary of the older cases. Differences between adult and childhood presentation are outlined and our patient is compared with prior reported cases. Case A 3-year-old girl presented with recurrent rectal blood loss caused by heterotopic gastric mucosa without duplication cyst. She was endoscopically treated with two-stage endoscopic surgical dissection (ESD). Up to now, rectal heterotopic gastric mucosa has been reported in 34 adults and 24 children, including this patient. There is an overall male dominance (69%). Presenting complaints in children were recurrent fresh blood loss per anum (96%), pain (46%), perineal ulcers (25%), diarrhoea (8%) and one patient had an ano-cutaneous fistula. Endoscopy revealed a mucosal elevation with a slightly different aspect (33%), a polyp (42%) and a solitary ulcer (25%). Endoscopy in adults reveals more frequently polyps compared to children. Treatment in childhood is mainly surgical where adults are more frequently treated with endoscopic techniques. Conclusion In a child with recurrent rectal bleeding in good general health, it is important to withhold heterotopic gastric mucosa in the differential diagnosis and take sufficient biopsies during endoscopy.

Knowledge of staff members of residential care facilities for individuals with intellectual disability on medication administration via enteral feeding tube.

BACKGROUND: Guidelines for the safe administration of drugs through enteral feeding tube (EFT) are an important tool to minimise the risk of errors. This study aimed to investigate knowledge of these guidelines among staff of residential care facilities (RCF) for people with ID. METHOD: Knowledge was assessed using a 13-item self-administered questionnaire. Questions reflected key aspects of guidelines on medication administration via EFT. All staff members that administer medication through EFT in Belgian RCFs were invited to participate (n = 553). RESULTS: Nine out of 10 RCFs participated, and 356 questionnaires were collected. Almost all participants were women (96%), and most (82%) had a non-nursing educational background. Mean self-perceived knowledge of medication administration via EFT was 6.7 (on a 0-10 scale). On average, 5.7 (SD 1.9) out of 13 questions were answered correctly. A nursing degree and previous education on medication administration via EFT were associated with significantly higher scores. Guideline recommendations regarding rinsing of used medicine cups (90% correct answers) and preparation of hard gelatin capsules (89%) were known best. Those regarding the use of protective equipment when crushing toxic substances (4% correct answers), crushing of sustained release and enteric-coated dosage forms (6%), elevation of the patient's backrest (14%) and flushing of the EFT (15%) were known the least. CONCLUSION: This study identified a substantial lack of knowledge of guidelines for drug administration through EFT among staff of RCFs for people with ID. Our findings call for tailored educational programmes in order to increase knowledge on this subject.

A case of chronic recurrent multifocal osteomyelitis associated with crohn's disease.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of unknown etiology, most commonly affecting the metaphysis of long bones, especially the tibia, femur and clavicle. The clinical spectrum varies from self-limited uni-or multi-focal lesions to chronic recurrent courses. Diagnosis is based on clinical, radiologic and pathological findings, is probably underdiagnosed due to poor recognition of the disease. A dysregulated innate immunity causes immune cell infiltration of the bones with subsequent osteoclast activation leading to sterile bone lesions. The molecular pathophyiology is still incompletely understood but association with other auto-inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, Wegener's disease, arthritis and synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is interesting. CRMO can precede the symptoms of the associated disease by several years. The bone remodeling caused by CRMO can cause permanent disability. We report the case of a 10-year-old boy with CRMO in association with Crohn's disease.

Algorithms for managing infant constipation, colic, regurgitation and cow's milk allergy in formula-fed infants.

UNLABELLED: Gastrointestinal symptoms, such as constipation, regurgitation and infant colic, occur in about half of infants. These symptoms are often functional, but they may also be caused by cow's milk protein allergy. We developed three algorithms for formula-fed infants, which are consensus rather than evidence-based due to the limited research available in the existing literature. CONCLUSION: We believe that these algorithms will help primary healthcare practitioners to recognise and manage these frequent gastrointestinal manifestations in infants.

Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells.

Calcineurin inhibitors (CNI), used frequently in solid organ transplant patients, are known to inhibit T cell proliferation, but their effect on humoral immunity is far less studied. Total and naive B cells from healthy adult donors were cultured in immunoglobulin (Ig)A- or IgG/IgE-promoting conditions with increasing doses of cyclosporin, tacrolimus, rapamycin or methylprednisolone. The effect on cell number, cell division, plasmablast differentiation and class-switching was tested. To examine the effect on T follicular helper (Tfh) cell differentiation, naive CD4(+) T cells were cultured with interleukin (IL)-12 and titrated immunosuppressive drug (IS) concentrations. Total B cell function was not affected by CNI. However, naive B cell proliferation was inhibited by cyclosporin and both CNI decreased plasmablast differentiation. Both CNI suppressed IgA, whereas only cyclosporin inhibited IgE class-switching. Rapamycin had a strong inhibitory effect on B cell function. Strikingly, methylprednisolone, increased plasmablast differentiation and IgE class-switching from naive B cells. Differentiation of Tfh cells decreased with increasing IS doses. CNI affected humoral immunity directly by suppressing naive B cells. CNI, as well as rapamycin and methylprednisolone, inhibited the in-vitro differentiation of Tfh from naive CD4(+) T cells. In view of its potent suppressive effect on B cell function and Tfh cell differentiation, rapamycin might be an interesting candidate in the management of B cell mediated complications post solid organ transplantation.

Raised immunoglobulin A and circulating T follicular helper cells are linked to the development of food allergy in paediatric liver transplant patients.

BACKGROUND: Post-transplant food allergy (LTFA) is increasingly observed after paediatric liver transplantation (LT). Although the immunopathology of LTFA remains unclear, immunoglobulin (Ig) E seems to be implicated. OBJECTIVE: To study humoral and cellular immunity in paediatric LT patients in search for factors associated with LTFA, and compare with healthy controls (HC) and non-transplant food-allergic children (FA). METHODS: We studied serum Ig levels in 29 LTFA, 43 non-food-allergic LT patients (LTnoFA), 21 FA patients and 36 HC. Serum-specific IgA and IgE against common food allergens in LTFA, IgA1 , IgA2 and joining-chain-containing polymeric IgA (pIgA) were measured. Peripheral blood mononuclear cells were analysed by flow cytometry for B and T cell populations of interest. RESULTS: Serum IgA and specific IgA were higher in LTFA compared to LTnoFA. LTFA patients had the highest proportion of circulating T follicular helper cells (cTfh). The percentage of cTfh correlated positively with serum IgA. Unique in LTFA was also the significant increase in serum markers of mucosal IgA and the decrease in the Th17 subset of CXCR5(-) CD4(+) cells compared to HC. Both LT patients exhibited a rise in IgA(+) memory B cells and plasmablasts compared to HC and FA. CONCLUSIONS: LT has an impact on humoral immunity, remarkably in those patients developing FA. The increase in serum markers of mucosal IgA, food allergen-specific IgA and cTfh cells observed in LTFA, point towards a disturbance in intestinal immune homoeostasis in this patient group.

Drug administration via enteral feeding tubes in residential care facilities for individuals with intellectual disability: an observational study.

BACKGROUND: The administration of oral medication to patients with an enteral feeding tube (EFT) is challenging. Compliance to guidelines concerning medication administration via EFT has been investigated extensively in the hospital setting. However, studies in residential care facilities (RCFs) for individuals with intellectual disability (ID) are very limited. Therefore, the present study aimed to collect direct observational data on drug administration practices to residents with EFT in multiple RCFs. METHOD: This cross-sectional, observational study was conducted in six Belgian RCFs for individuals with ID. Observations of medication preparation and administration through EFT were carried out in two randomly selected units per participating RCF, on 2 days per unit during all daytime drug rounds, using a direct observation method. Afterwards, the recorded observations were compared with international guidelines on drug preparation and administration through EFT. RESULTS: In total, 862 drug preparations and 268 administrations in 48 residents with EFT were witnessed. Mixing together multiple drugs, not diluting liquid formulations with at least an equal amount of water, not shaking suspensions/emulsions before use, and not selecting the most appropriate dosage form were the most common deviations from medication preparation guideline recommendations. For medication administration, not flushing the EFT with at least 15 mL water was the most common deviation. We also observed high variability in working methods regarding medication preparation and administration via EFT, even between staff members of the same unit. CONCLUSION: This study found that current guidelines concerning medication preparation and administration through EFT are often not followed in Belgian RCFs for individuals with ID. Further research aimed at understanding why current guidelines are not followed seems warranted.

Gastrostomy use in children: a 3-year single centre experience.

AIM: Monocentric retrospective paediatric study describing indications for gastrostomy and major complications, compared to literature data as part of a quality check. METHODS: Records of all gastrostomy patients consulting at the UZ Ghent paediatric gastro-enterology department between January 2007-December 2009 were reviewed in December 2010 regarding indication, age and weight at tube insertion, insertion method, major complications and current gastrostomy tube type. RESULTS: 178 patients were included of which 165 (93%) were placed using the endoscopic pull technique, the others were placed surgically (n = 13). Neurodevelopmental disability with oral motor dysfunction was the major indication (113, 63%). Other indications were failure to thrive due to concomitant disease (65, 37%). Median age at tube insertion was 3yr (interquartile range (IQR) 0.6-9) with median tube time of 3.9 yr (IQR 1.9-7.2). Immediate complications were 1 peritonitis and 1 post-insertion fever episode. Late complications (10, 5.6%) were 1 gastrocolic fistula, 1 dislocation and 8 buried bumpers after 4 yr (range 35-10.4) of tube insertion. The incidence of buried bumper increased significantly with increasing PEG tube time (P < 0.01). Gastro-oesophageal reflux disease (GORD) led to Nissen fundoplication in 45 (25.3%) patients. The proportion of patients receiving a fundoplication remained about 20% over time but the time lapse between the 2 procedures decreased significantly. CONCLUSION: The development of buried bumper is associated to prolonged PEG tube use. In case of important GORD laparoscopic Nissen procedure and PEG placement can be performed simultaneously without increasing complication rate.

Nutritional support in children with neurodevelopmental disabilities. Proceedings Bespghan Meeting, Ghent December 2011.

Feeding difficulties, mainly determined by oral motor problems, are common in patients with severe neurodevelopmental disabilities (NDD). These problems have a negative impact on health and developmental outcome as a consequence of insufficient intake. Research data show that insufficient intake, and not enhanced caloric needs, is the major cause of malnutrition. However, no direct relation between intake and nutritional state has been shown, illustrating the wide variety in caloric needs in this population. Individual caloric needs in patients with NDD show a wide variety, but are generally lower than in normal children. Treatment of these patients is complex as data on adequate daily allowances for this population are not available and standard anthropometric cut-off points to define malnutrition need adaptation. In order to prevent and treat malnutrition in patients with neurodevelopmental problems, careful multidisciplinary follow-up is indicated, aimed at early detection of feeding problems, nutritional deficiencies and growth failure. Oral food intake can be enhanced using adapted food texture and special feeding devices, giving positional support combined with specialized dietary advice on nutrient- and caloric-dense food. When oral feeding is unsafe or inefficient, partial or total enteral nutrition is started through a gastrostomy, with or without concomitant fundoplication. Evidence based criteria guiding this decision are lacking.

Anal canal duplication in an 11-year-old-child.

Anal canal duplication (ACD) is the least frequent digestive duplication. Symptoms are often absent but tend to increase with age. Recognition is, however, important as almost half of the patients with ACD have concomitant malformations. We present the clinical history of an eleven-year-old girl with ACD followed by a review of symptoms, diagnosis, treatment, and prognosis based on all the reported cases in English literature.

Colon transit time and anorectal manometry in children and young adults with spina bifida.

PURPOSE: This study evaluates colon transit time (CTT) and anorectal manometry (ARM) in spina bifida (SB) patients in relation to the level of lesion, mobility, constipation, and continence status. METHODS: SB patients between 6 and 19 years, who are not using antegrade continence enemas and followed at the SB Reference Centre UZ Ghent, were asked to participate. Medical history was retrospectively retrieved from the medical file. Stool habits were prospectively collected using standardized questionnaires. CTT was measured using the 6-day pellet abdominal X-ray method. ARM was performed in non-sedated children with a water-perfused, latex-free catheter. RESULTS: Forty out of 52 eligible patients consented to perform CTT, of which 19 also performed the ARM. Fifteen (37 %) SB patients were constipated despite treatment. Twenty-six (65 %) were (pseudo) continent. The total CTT was significantly prolonged in SB patients (median CTT 86.4 vs. 36 h controls). The CTT was significantly prolonged in constipated SB patients compared to non-constipated SB patients (122.4 vs. 52.8 h). Spontaneously continent patients had a normal CTT (33.6 h) as well as a significantly higher resting pressure compared to the pseudo-continent and incontinent SB patients (resting pressure 56.5 vs. 32.5 mmHg). An abnormal CTT was associated with a treatment necessity to achieve pseudo-continence (p = 0.006). CONCLUSION: CTT in SB patients was significantly prolonged, indicating a neurogenic involvement of the bowel and slow transit constipation. SB patients with a normal CTT and a normal ARM spontaneously achieved fecal continence. CTT can help tailor the continence therapy in SB patients.

Colon transit time in healthy children and adolescents.

PURPOSE: The aims of this study are to describe normal colon transit time (CTT) in healthy children, correlate results with age, the Bristol stool scale, and stool frequency, and to evaluate intra- and interobserver variability. METHODS: Inclusion criteria were as follows: healthy children between 3 and 18 years old with a normal defecation pattern, no history of abdominal surgery, and no medication use. Total and segmental CTT is measured by taking ten polythene radiopaque markers during six consecutive days followed by a single abdominal X-ray on day 7. Total and segmental CTT are calculated by multiplying the number of markers by 2.4 (Abrahamsson et al. Scand J Gastroenterol 32:72-80, 1988). RESULTS: Fifty-four children and adolescents have participated: 30 boys and 24 girls (median age 10 years (3-18 years)). Median total CTT is 36 h (<2.4-86.4 h). There is no significant difference for age category (toddlers 31.2 h (<2.4-74.4 h), elementary school 36 h (2.4-79.2 h), and adolescents 43.2 h (14.4-86.4 h)). Segmental CTT reveals a median right colon CTT of 4.8 h (0-28.8 h); a median left colon CTT of 2.4 h (0-31.2 h); and a median rectosigmoidal CTT of 24 h (0-64.8 h). The Bristol stool scale correlates with total CTT (p = 0.031). The intra- and interobserver variability displays an ICC of 0.999 for the total CTT. CONCLUSION: The CTT of normal healthy children is not sex- or age-related (above the age of 3 years). The Abrahamson method for CTT measurement by using bony landmarks for the determination of colon segments is easy to perform and well tolerated with a virtual inexistent rating difference between different observers.

[Colon transit time in children and young adults with open spinal dysraphism]. / Temps du transit colique chez l'enfant atteint de dysraphisme ouvert.

INTRODUCTION: Patients with open spinal dysraphism (OSD) frequently present constipation and incontinence requiring treatment. AIM: Evaluation of colon transit time (CTT) in patients with OSD, in relation to neural lesion, mobility, bowel habits, and continence status. METHODS: OSD patients aged between 6 and 20 years, who did not use antegrade enemas, were invited to participate in the study. Data from the medical file and information retrieved by questionnaires for constipation and incontinence were collected. The control group consisted of 13 healthy age-matched children. CTT was measured using the 6-day pellet method with an abdominal X-ray on day 7. Laxatives were continued and retrograde colon enemas were stopped 48h prior the X-ray. RESULTS: Thirty of the 33 patients who met the inclusion criteria agreed to participate. Twelve (40%) patients were constipated (Rome III criteria) despite treatment. Fifteen (50%) were continent, with or without treatment. Total CTT was significantly longer in OSD patients (median CTT: 86.4h vs. 43.2h controls). Constipated OSD patients had a significantly prolonged CTT compared to non-constipated patients (CTT: 125.4h vs. 51.6h). Spontaneous continent OSD patients had a normal CTT (CTT: 33.6h). An abnormal CTT predicted the necessity of treatment to achieve continence (P<0.006). CONCLUSION: CTT in OSD patients is significantly prolonged, indicating a neurogenic involvement of the bowel and a slow transit constipation. An abnormal CTT predicts the necessity of therapy to achieve fecal continence.

Colon enemas for fecal incontinence in patients with spina bifida.

PURPOSE: We studied the use of colon enemas in achieving fecal pseudocontinence in patients with spina bifida to define the variables associated with success. MATERIALS AND METHODS: Questionnaires were individually filled out by all patients with spina bifida using colon enemas at our Spina Bifida Reference Center between October 2009 and June 2010. Patient age, type of enema, volume required, evacuation time, followup, continence and independence were recorded. Fecal pseudocontinence was defined as no involuntary stool loss during the last 6 months. Social continence was defined as involuntary stool loss less than once monthly. Children are routinely seen at the reference center, while adults are seen on request. RESULTS: A total of 25 children and 15 adults with spina bifida were studied. Median volume required was 1 liter (range 0.5 to 2) in children and 1.5 liters (0.75 to 3) in adults. Median evacuation time was 30 minutes (range 15 to 60) in children and 60 minutes (30 to 120) in adults. Fecal continence was achieved in 76% of children (19 of 25) and 60% of adults (9 of 15), and social continence in 88% of children (23 of 25) and 67% of adults (10 of 15). A significant relation was found between medical followup since childhood and fecal pseudocontinence. No enema determinants predicted pseudocontinence. CONCLUSIONS: Colon enemas are a valuable method in achieving continence. At our center medical followup from childhood to adulthood is associated with successful acquisition of fecal pseudocontinence.

Multiple magnet ingestion: a real challenge for the paediatric surgeon.

The paediatric population aged 1-3 years represents about 80% of patients presenting with foreign body ingestion. Only 10 to 20% of ingested foreign bodies will fail to pass through the entire gastrointestinal tract. The decision to remove them is based on location, size and nature of the foreign body. In particular, ingestion of multiple magnets or magnets and other metallic objects require a more aggressive management.