Management guidelines of eosinophilic esophagitis in childhood.

OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor-responsive esophageal eosinophilia. This position paper aims at providing practical guidelines for the management of children and adolescents with EoE. METHODS: Relevant literature from searches of PubMed, CINAHL, and recent guidelines was reviewed. In the absence of an evidence base, recommendations reflect the expert opinion of the authors. Final consensus was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved for severe symptoms requiring rapid relief or where other treatments have failed. Esophageal dilatation is an option in children with EoE who have esophageal stenosis unresponsive to drug therapy. Maintenance treatment may be required in case of frequent relapse, although an optimal regimen still needs to be determined. CONCLUSIONS: EoE is a chronic, relapsing inflammatory disease with largely unquantified long-term consequences. Investigations and treatment are tailored to the individual and must not create more morbidity for the patient and family than the disease itself. Better maintenance treatment as well as biomarkers for assessing treatment response and predicting long-term complications is urgently needed.

A practical guide for the diagnosis of primary enteric nervous system disorders.

OBJECTIVE: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field. RESULTS: Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance. CONCLUSIONS: The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values.

[Treatment perspectives]. / Les perspectives thérapeutiques.

Celiac disease (CD) is a chronic inflammatory enteropathy caused by the ingestion of gluten. A safe and efficient but unpleasant treatment exists for CD in form of a strict gluten-free diet. Thus, there is a need for new treatment strategies, which are based on the improved and advanced understanding of the pathophysiology of CD. The first strategy consists in reducing or even eliminating major antigenic motifs in gluten, responsible for the inflammatory reaction. The use of less immunogenic wheat was suggested but this seems rather difficult to realize. However, a complete digestion of the immunogenic parts of gluten looks very promising. This can be obtained by the use of polymers, capable to sequester gluten proteins or even better via the exogenous administration of propyl-endopeptidases, with two different enzymes under development. Another approach could be the use of inhibitors of tissue transglutaminase, a strategy which is under clinical investigation. Alternatively, inhibition of the site of liaison of immunostimulatory peptides with HLA molecules was suggested and is also under investigation in vivo. For patients suffering from refractory sprue, the inhibition of IL15 might be of therapeutic interest with the hope to improve the fatal outcome of many of these patients. However, the ultimate treatment approach is in form of prevention and the role of infectious agents, such as Rotavirus, in disease onset has to be considered.

Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines.

OBJECTIVES: This guideline provides recommendations for the diagnosis and management of suspected cow's-milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence-based guidelines on CMPA. DIAGNOSIS: If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life-threatening reaction with a positive test for CMP-specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA. TREATMENT: In breast-fed infants, the mother should start a strict CMP-free diet. Non-breast-fed infants with confirmed CMPA should receive an extensively hydrolyzed protein-based formula with proven efficacy in appropriate clinical trials; amino acids-based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion. REEVALUATION: Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.

Cutaneous manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.

BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder characterized by neonatal autoimmune enteropathy, diabetes and thyroiditis, food allergies and skin rash. IPEX syndrome is caused by mutations in FOXP3, a master control gene of regulatory T cells (Tregs), resulting in absent or dysfunctional Tregs. Data in the literature are scarce and the cutaneous manifestations are rarely depicted. OBJECTIVES: To evaluate the frequency and characteristics of cutaneous manifestations found in IPEX. METHODS: Retrospective single-centre study of a case series of IPEX. Patients' data were retrieved from medical files and numerous parameters concerning general and cutaneous characteristics of the disease were recorded. RESULTS: Ten children with IPEX were studied. Cutaneous involvement was present in seven of 10 children; age at onset was 0-4 months, median 1.5. All patients presented with atopic dermatitis (AD). Three presented more psoriasiform lesions. Eczema was severe; most affected areas were lower limbs, trunk and face. Pruritus was present in four of seven, and painful fissurary cheilitis in four of seven. Hyper-IgE was found in seven of 10 and hypereosinophilia in five of 10. Skin biopsies showed eczematiform or psoriasiform features. Affected patients were improved by dermocorticoids; no clear improvement was obtained with immunosuppressive regimens. Other features were urticaria secondary to food allergies and staphylococcal sepsis, mostly Staphylococcus aureus and catheter related. CONCLUSIONS: AD seems to be a frequent finding in IPEX syndrome, which is characterized by Treg anomalies. This hints to a possible role of Tregs in AD, which is then discussed in this study.

Clinical evidence for immunomodulatory effects of probiotic bacteria.

Close, tightly orchestrated interactions between the intestinal epithelium and the mucosa-associated immune system are critical for normal intestinal absorptive and immunological functions. Recent data indicate that commensal intestinal microbiota represents a major modulator of intestinal homeostasis. This review analyzes the process of intestinal colonization and the interaction of microbiota with the intestinal epithelium and mucosal immune system, with special reference to the first years of extrauterine life. Dysregulation of the symbiotic interaction between intestinal microbiota and the mucosa may result in a pathological condition with potential clinical repercussions. Based on the concept that there is a beneficial and symbiotic relation between the host and endogenous microbiota, strategies aimed at directly modulating intestinal microbiota with regard to disease prevention or treatment have been developed. One strategy involves administering viable probiotic bacteria. Clinical evidence for the beneficial effect of probiotics in the prevention and/or treatment of necrotizing enterocolitis, infectious and antibiotic-associated diarrhea, allergic diseases, and inflammatory bowel disorders is reviewed herein.

Long-term outcome, growth and digestive function in children 2 to 18 years after intestinal transplantation.

OBJECTIVE: Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognised alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analysed graft functions in 31 children after SBTx with a follow-up of 2-18 years (median 7 years). PATIENTS: Twelve children had isolated SBTx, 19 had combined liver-SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2-3 years post-Tx. RESULTS: All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84-89%. Growth parameters revealed at transplantation a mean height Z-score of -1.17. After Tx, two-thirds of children had normal growth, whereas in one-third, Z-scores remained lower than -2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in non-compliant patients. Five intestinal grafts were removed 2.5-8 years post-Tx for acute or chronic rejection. CONCLUSIONS: This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important pre-requisite for long-term graft function.

Clinical Heterogeneity of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A French Multicenter Retrospective Study.

OBJECTIVE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disease caused by mutations in the forkhead box protein 3 gene (FOXP3), which encodes a key regulator of immune tolerance. The aim of this study was to describe the clinical heterogeneity of the disease in a national French cohort. METHODS: Multicenter retrospective study of patients diagnosed with IPEX syndrome caused by mutations in FOXP3. RESULTS: Thirty children from 26 families were included. Age at disease onset (median [first to third quartile]) was 1.5 mo [0-84] and at death 3.5 years [0-10.5] (n = 15) indicating a high heterogeneity. Initial presentation was diarrhoea (68%), type 1 diabetes (T1D; 25%), skin lesions (7%) and nephropathy (3%). During the course of the disease the following main symptoms were observed: diarrhoea (100%), skin lesions (85%), T1DM (50%), severe food allergies (39%), haematological disorders (28%), nephropathies (25%), hepatitis (14%) as well as the presence of a variety of autoantibodies. Immunosuppressive mono- or combination therapy led to improvement in eight children. Three boys displayed a stable disease course without any immunosuppressive medication. Overall 10-year survival rate was 43% (42% in transplanted patients and 52% in patients on immunosuppressive therapy). Five out of 22 identified FOXP3 mutations have not been described yet: c.-23 + 1G > A, c.-23 + 5G > A, c.264delC, c.1015C > T and c.1091A > G. The first two produced atypical, attenuated phenotypes. Missense and frameshift mutations affecting the forkhead domain were associated with poor survival (Gehan-Wilcoxon p = 0.002). CONCLUSION: The broad phenotypic heterogeneity of IPEX raises questions about modifying factors and justifies early FOXP3 sequencing in suspected cases.

Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN.

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.

Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study.

BACKGROUND: Immunosuppressors play a major role in maintaining remission in Crohn's disease (CD). In patients who do not tolerate or escape therapy with azathioprine (AZA)/6-mercaptopurine, there is a marked need for other immunosuppressive drugs. The aim of the present study was to evaluate the efficacy and safety of methotrexate (MTX) in children with active CD. METHODS: In a retrospective multicenter (n = 3) study, the efficacy of MTX to induce complete remission or a clinical improvement was analyzed in 61 children with active CD. RESULTS: CD was diagnosed at a mean age of 11.1 +/- 2.3 years, and MTX was introduced 3.1 +/- 2.2 years after diagnosis. Indications to use MTX were a nonresponse to or relapse under AZA (n = 42) or AZA intolerance/toxicity (n = 19). MTX improved or induced complete remission in 49 patients (80%), of whom 18 (29.5%) relapsed after 13 +/- 10 months of treatment. Under MTX medication, complete remission was observed in 39%, 49%, and 45% at 3, 6, and 12 months, respectively. Follow-up over at least 24 months in 11 children confirmed a sustained remission on MTX monotherapy up to 40 months. Adverse reactions were observed in 14 patients (24%), requiring discontinuation of MTX in 6 children (10%) (liver enzyme elevation, n = 2; varicella-zoster, n = 1; nausea, n = 3). MTX allowed corticosteroid discontinuation in 36 patients. CONCLUSIONS: MTX improved the clinical course in most pediatric CD patients who escaped or did not tolerate AZA. Short-time toxicity of MTX resulted in drug discontinuation in <10%. These data point to a beneficial and safe use of MTX in the treatment of pediatric CD.

Metabolism of glycosyl ureides by human intestinal brush border enzymes.

13C-labeled glycosyl ureides were recently proposed as a new marker of the orocecal transit time: after passing the small bowel the sugar-urea bond is split by bacterial allantoicase. Further degradation results in 13CO2 which can be measured in the exhaled breath. The aim of this study was to detect an eventual allantoicase-like activity in the human gut and to elucidate the metabolism of glycosyl ureides by human intestinal brush border enzymes. Biopsies of 15 duodenal specimen and 6 colon specimen were homogenised and incubated with several disaccharides and their corresponding disaccharide ureides under various experimental conditions. Hydrolysis of the sugar-urea bond could not be observed neither in the small bowel nor in the colon. However, the conjugation between the two sugars was split. In a modified Dahlqvist assay lactase showed the same kinetics with lactose and lactose ureide as substrates whereas maltose showed a significantly 2.6-fold higher affinity to maltase than maltose ureide (P < 0.001). No major difference between these two substrates could be detected when total maltase activity was inhibited by acarbose. In summary, the human gut tissue possesses no allantoicase-like activity. Therefore, glycosyl ureides seem to be appropriate substances to test the orocecal transit time.

Butyrate mediates Caco-2 cell apoptosis via up-regulation of pro-apoptotic BAK and inducing caspase-3 mediated cleavage of poly-(ADP-ribose) polymerase (PARP).

Butyrate exerts potent anti-tumor effects by inhibiting cancer cell growth and inducing apoptosis. However, the molecular mechanisms mediating these effects remain largely unknown. Using the Caco-2 cell line, a well established model of colon cancer cells, our data show that butyrate induced apoptosis (maximum 79%) is mediated via activation of the caspase-cascade. A key event was the proteolytic activation of caspase-3, triggering degradation of poly-(ADP-ribose) polymerase (PARP). Inactivation of caspase-3 with the tetrapeptide zDEVD-FMK completely inhibited the apoptotic response to butyrate. In parallel, butyrate potently up-regulated the expression of the pro-apoptotic protein bak, without changing Caco-2 cell bcl-2 expression. Butyrate-induced Caco-2 cell apoptosis was completely blocked by the addition of cycloheximide, indicating the necessity of protein synthesis. However, when this inhibitor was added at a time point where bak expression was already enhanced (12 - 16 h after butyrate stimulation), it failed to protect Caco-2 cells against apoptosis. Taken together, these data provide evidence that the molecular events involved in butyrate induced colon cancer cell apoptosis include the caspase-cascade and the mitochondrial bcl-pathway.

[Hematemesis in an 11-month-old child: an unusual symptom revealing a foreign body in the stomach]. / Hématémèse chez un enfant de 11 mois: un mode de révélation rare d'un corps étranger intragastrique.

Ingestion of foreign body has often no consequence. We report on a case in an 11-month-old girl who was referred for mild hematemesis and anorexia. Upper digestive tract endoscopy found a small metallic foreign body in the gastric antrum. After its removal, all symptoms disappeared. It is usually recommended to remove foreign bodies by endoscopy when they are in esophageal position, or are more than 3 to 5 cm long, or have a shape that may hurt the gut mucosa. Although rare, a gastric foreign body should be searched for in face of an upper gastrointestinal bleeding in an infant.

The effect of inflammation severity and of treatment on the production and release of TNFalpha by colonic explants in inflammatory bowel disease.

BACKGROUND: Despite its pivotal role in mucosal inflammation, data on TNFalpha levels in inflammatory bowel diseases have been contradictory. AIM: To examine TNFalpha production in relation to the type and severity of inflammation and therapy, using colonic explant cultures. MATERIALS AND METHODS: Rectal mucosal biopsies from 271 paediatric patients (178 inflammatory bowel disease, 27 inflammatory controls, 66 normal) were cultured for 4 or 18 h. Basal TNFalpha tissue content and release into the medium were measured by ELISA and compared to histological severity and clinical parameters. RESULTS: TNFalpha release as well as tissue-associated TNFalpha levels were significantly increased in rectal biopsies from involved inflammatory bowel disease tissue. The amount of TNFalpha correlated with inflammation severity scores. TNFalpha levels were higher at 18 compared to 4 h in all groups, whether inflamed or not. TNFalpha released from rectal biopsies was lower among treated patients at 18 h. The presence of proximal colonic involvement was associated with higher TNFalpha release by uninvolved Crohn's disease rectal biopsies compared to patients with ileitis alone. CONCLUSIONS: TNFalpha production and release is increased in involved rectal explants from inflammatory bowel disease. Anti-inflammatory treatment diminishes this response.

Dexamethasone inhibits IFNgamma-induced MHC class II expression of intestinal epithelial cells independently of the TGF-beta1 regulatory pathway.

BACKGROUND: In the presence of inflammation, an increased expression of enterocyte MHC class II is observed, leading to altered mucosal antigen handling. Corticosteroids are potent anti-inflammatory drugs, widely used in treating inflammatory bowel disorders. However, their diverse mechanisms of action are only partially understood. AIM: To evaluate effect and mechanisms of corticosteroids on intestinal crypt epithelial cell MHC class II. METHODS: The effect of dexamethasone treatment on cytokine-induced MHC class II expression was measured in IEC-6 cells by immunofluorescence and flow cytometry. To determine the role of the TGF-beta1 regulatory pathway in mediating the effects of dexamethasone, neutralizing anti-TGF-beta antibodies were used. Additionally, endogenous and dexamethasone-stimulated IEC-6 cell TGF-beta1 production was measured by ELISA. RESULTS: Dexamethasone potently down-regulated IFNgamma-induced class II expression on IEC-6 cells, in a dose-dependent manner. TGF-beta1 had a similar inhibitory effect on class II expression. However, neutralizing anti-TGF-beta antibodies did not alter the effect of dexamethasone. Furthermore, dexamethasone reduced endogenous TGF-beta1 synthesis. CONCLUSIONS: Corticosteroids inhibit cytokine-induced MHC class II expression on IEC-6 cells in a TGF-beta1 independent way. This effect may markedly alter enterocytic antigen presentation, reducing the aberrant state of activation of mucosal immune cells.

Predictors of response to infliximab in paediatric perianal Crohn's disease.

BACKGROUND: It is reported that 27-54% of paediatric patients with perianal Crohn's disease (CD) do not respond to infliximab (IFX). AIM: To identify predictors of response to IFX in paediatric perianal CD. METHODS: A retrospective cohort study of 101 paediatric patients treated with IFX between 2000 and 2011 for perianal CD in 22 French hospitals of the GETAID pédiatrique network was performed. Response was monitored after induction therapy and at 1 year. Complete response was defined by closure of all fistulas and complete healing of ulcers. Associations between baseline characteristics and (i) 1-year response and (ii) time of first relapse among initial responders were tested by logistic regression and Cox model respectively. RESULTS: Eighty-nine patients (88%) responded to induction therapy (36 partial/53 complete). At 1 year, 76 patients (75%) were responders (22 partial/54 complete). Predictors of 1-year response were: number of fistulas ≤1 (OR: 3.76, 95% CI: 1.20-11.77, P = 0.03) and baseline Harvey-Bradshaw index <5 (OR: 3.72, 95% CI: 1.10-12.60, P = 0.03). Predictors of relapse among initial responders were: CD duration <10 months (OR: 3.31, 95% CI: 1.34-8.19, P = 0.0097) and number of fistulas >1 (OR: 2.79, 95% CI: 1.12-6.95, P = 0.028). Combined therapy with an immunomodulator was not associated with 1-year response or time of relapse. CONCLUSION: Those patients with perianal Crohn's disease have better outcomes if they have less fistulas, a low baseline Harvey-Bradshaw Index or a longer duration of Crohn's disease.

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease.

Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

Compartmentalized expression of Th1 and Th17 cytokines in pediatric inflammatory bowel diseases.

BACKGROUND: Interleukin (IL)-23, IL-17A, IL-17F, and interferon-gamma (IFN-γ) are important mediators of inflammatory colitis and are potential therapeutic targets in inflammatory bowel disease (IBD). Their expression profile in the different parts of normal noninflammatory intestine is unclear and their changes during pathology have not yet been addressed in pediatric IBD patients. METHODS: We quantified the transcriptional expression of IL-23, IL-12, IL-17A, IL-17F, IL-6, and IL-10 in healthy, noninflammatory duodenum, ileum, and colon and in inflamed and noninflamed biopsies of pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: In healthy tissue, expression of IL-17A is highest in the ileum, with IFN-γ expression lowest in the colon. Compared to healthy sections, CD patients displayed increased IL-12p35 and IFN-γ levels in noninflamed ileum and colon, respectively. Modifications of cytokine expression between noninflamed and inflamed tissues was characterized by increased IL-17A in UC colon, IFN-γ in CD colon, and IL-17A, IFN-γ and IL-6 in CD ileum. Elevated IL-17A levels were positively correlated with IFN-γ in both inflammatory CD and UC but IL-17A and IFN-γ were correlated with IL-23p19 in CD ileum only. CONCLUSIONS: The expression of Th1 and Th17 cytokines varies along the intestine, indicating local specific regulation mechanisms. However, the cytokine expression patterns in the same tissue depends on the pathology, with a Th1 or a Th17 profile in the colon of CD and UC patients, respectively, and a Th1/Th17 profile in the ileum of CD patients. This indicates overlapping but distinct immune mechanisms driving intestinal inflammation in these two pathologies.

[Diagnosis of hypochromic microcytic anemia in children]. / Exploration d'une anémie microcytaire chez l'enfant.

Iron deficiency is the most frequent cause of hypochromic microcytic anemia in children, but other causes, some of them requiring specific management, may be involved. Checking the iron-status is absolutely mandatory. When iron-status parameters are low, inadequate intake, malabsorption, blood loss, and abnormal iron utilization must be tested. In absence of iron deficiency, α- and ß-globin and heme biosynthetic gene status must be checked. Assessing the iron stock level is difficult, because there is an overlap between the values observed in iron-replete and iron-deprived patients, so that at least 2 iron-status parameters must be below normal for diagnosing iron deficiency. Furthermore, inflammation may also mimic some characteristics of iron deficiency. Diagnosing iron deficiency leads to prescribing iron supplementation with follow-up at the end and 3 months after cessation of treatment. When iron stores are not replete at the end of treatment, compliance and dosage must be reevaluated and occult bleeding sought. The latter is also required when the iron store decreases 3 months after cessation of iron replacement.

The efficacy of exclusive nutritional therapy in paediatric Crohn's disease, comparing fractionated oral vs. continuous enteral feeding.

BACKGROUND: Nutritional therapy has an established role as induction therapy in paediatric Crohn's disease. However, compliance is the main difficulty and may be greatly influenced by the administration route. AIM: To analyse the efficiency of exclusive nutrition to induce remission in children with Crohn's disease comparing fractionated oral vs. continuous enteral feeding. METHODS: The medical records of 106 patients treated by exclusive nutritional therapy [Modulen IBD (R)] by either oral or continuous enteral route were reviewed retrospectively. Comparative analyses of remission rates, changes in anthropometry, Paediatric Crohn's disease Activity Index (PCDAI), laboratory indices and compliance rates were performed. RESULTS: On exclusive enteral nutrition, at 8 weeks, 34/45 patients achieved remission in the oral group (75% on intention-to-treat analysis) and 52/61 (85%) in the enteral nutrition group (P = 0.157). All patients showed a significant decrease in disease severity assessed by PCDAI (P < 0.0001) and significant improvements in anthropometric measures and inflammatory indices. No difference was observed whether Modulen IBD was administered orally or by continuous enteral feeding, apart from weight gain, which was greater in the enteral group (P = 0.041). In a subgroup of patients, mucosal healing was evidenced on follow-up endoscopies showing a clear correlation to remission. Compliance rates (87% and 90%) were similar. Nevertheless, noncompliant patients had lower mucosal healing and remission rates. CONCLUSIONS: These retrospective data suggest that the use of fractionated oral nutritional therapy might be as efficacious as continuous enteral administration to induce remission and mucosal healing in children with Crohn's disease. However, appropriate prospective clinical trials are needed to confirm these findings.