Duodenal stenosis, an unusual presentation of eosinophilic gastroenteritis: a case report.

Eosinophilic gastrointestinal diseases (EGIDs) are rare, chronic inflammatory disorders characterized by eosinophilic infiltration of the gastrointestinal tract. Symptoms and clinical presentations vary depending on the site and layer of the gastrointestinal wall infiltrated by eosinophils. Gastrointestinal obstruction is a serious, though uncommon, presentation. Management can be extremely challenging because of the rarity of the condition and the lack of robust scientific evidence. Current treatment approaches for EGIDs mainly focus on elimination diets, proton pump inhibitors and corticosteroids, which present high refractoriness rates. Novel targeted therapies are being investigated but not routinely used. Surgery should be avoided as far as possible; however, it may be the only option in gastrointestinal obstruction when long-term remission cannot be attained by any medical strategy. Herein we report the case of an adolescent boy affected by an eosinophilic gastrointestinal disease with progressive duodenal stenosis, refractory to medical therapy, who successfully benefitted from surgical management. He presented with a one-year history of gastrointestinal obstructive symptoms with feeding intolerance. After the diagnostic workup, he was diagnosed with an eosinophilic gastrointestinal disease (esophagitis and enteritis) with a duodenal involvement causing a progressive duodenal stenosis. Due to refractoriness to the conventional medical therapies and the consequent high impact on his quality of life, related both to the need for enteral nutrition and repeated hospitalizations, we decided to perform a gastro-jejunum anastomosis, which allowed us to obtain a clinical and endoscopic long-term remission. The early discussion of the case and the involvement of all experienced specialists, pediatricians and pediatric surgeons is essential.

Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective.

Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march.

Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease.

BACKGROUND: Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. METHODS: This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. RESULTS: Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). CONCLUSIONS: Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

Associations between early life stress and anterior pituitary gland volume development during late childhood.

Early Life Stress (ELS) is thought to influence Hypothalamic-Pituitary-Adrenal-Axis (HPAA) functioning, contributing to an increased risk for psychopathology through dysregulation of biological stress responses. Research exploring relationships between ELS and HPAA functioning has largely focused on its key hormonal output, cortisol. However, findings have been inconsistent, potentially due to cortisol's distinctive diurnal patterns and dynamic nature complicating its accurate measurement. Thus, this study explored the link between ELS and a more stable, structural component of the HPAA, specifically, anterior pituitary gland volume (PGV) in a community sample of children (N = 129, 68 female). PGV was traced from Magnetic Resonance Imaging brain scans across two time-points at ages 8 (baseline) and 10 years (follow-up). ELS exposure was assessed at baseline through parent-report questionnaires and maternal affective behavior observed in mother-child interaction tasks. ELS variables were reduced to a 5-factor structure using exploratory factor analysis - Uninvolved Parenting, Negative Affective Parenting, Neglect, Trauma, and Dysfunctional Discipline. Direct and sex-moderated associations between ELS and PGV were explored using regression and linear mixed models analyses. PGV-mediated associations between ELS and internalizing symptoms were also investigated. Childhood Neglect was significantly associated with greater baseline anterior PGV, that was stable over the follow-up period. This effect was found in the whole sample, and in males, specifically. No mediation effects were found. Results suggest that neglect may play a unique role in HPAA neurodevelopment; however, it is important that future research extends into adolescence to more clearly characterize these neurodevelopmental associations and any subsequent psychopathological outcomes.

Biological therapy in pediatric age.

Biological therapies, especially blocking tumor necrosis factor-α (TNFα) agents have radically changed the therapeutic approach and disease course of pediatric inflammatory bowel disease (IBD). In particular, drugs such as infliximab (IFX) and adalimumab (ADA) have been demonstrated to be effective in inducing and maintaining corticosteroid-free remission in both adult and pediatric patients with Crohns Disease (CD) and Ulcerative colitis (UC). Biosimilar biological (BioS) therapy is increasingly being used in pediatric age even though most knowledge on the safety and efficacy of these agents is based on IFX in adult IBD data. Studies show high rates of clinical response and remission in both IFX naïve patients and in patients switched from originator to BioS with similar risks of adverse events (AEs) as those reported with IFX originator. In the present review indications, efficacy and AEs of biological therapy in pediatric IBD will be discussed, as well as the role of other biological agents such as Golimumab, Vedolizumab and Ustekinumab, the role of BioS biological therapy and utility of therapeutic drug monitoring in clinical practice.

Thiopurine metabolites variations during co-treatment with aminosalicylates for inflammatory bowel disease: effect of N-acetyl transferase polymorphisms.

AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate (5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase (NAT) 1 and 2. METHODS: Concentrations of thioguanine nucleotides (TGN) and methymercaptopurine nucleotides (MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients (3 females and 9 males, median age 16 years) with inflammatory bowel disease (6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines (7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. DNA was extracted and genotyping of NAT1, NAT2, inosine triphosphate pyrophosphatase (ITPA) and thiopurine methyl transferase (TPMT) genes was performed using PCR assays. RESULTS: Median TGN concentration before 5-ASA interruption was 270 pmol/8 x 10(8) erythrocytes (range: 145-750); after the interruption of the aminosalicylate, a 35% reduction in TGN mean concentrations (absolute mean reduction 109 pmol/8 × 10(8) erythrocytes) was observed (median 221 pmol/8 × 10(8) erythrocytes, range: 96-427, P value linear mixed effects model 0.0011). Demographic and clinical covariates were not related to thiopurine metabolites concentrations. All patients were wild-type for the most relevant ITPA and TPMT variants. For NAT1 genotyping, 7 subjects presented an allele combination corresponding to fast enzymatic activity and 5 to slow activity. NAT1 genotypes corresponding to fast enzymatic activity were associated with reduced TGN concentration (P value linear mixed effects model 0.033), putatively because of increased 5-ASA inactivation and consequent reduced inhibition of thiopurine metabolism. The effect of NAT1 status on TGN seems to be persistent even after one month since the interruption of the aminosalicylate. No effect of NAT1 genotypes was shown on MMPN concentrations. NAT2 genotyping revealed that 6 patients presented a genotype corresponding to fast enzymatic activity and 6 to slow activity; NAT2 genotypes were not related to thiopurine metabolites concentration in this study. CONCLUSION: NAT1 genotype affects TGN levels in patients treated with thiopurines and aminosalicylates and could therefore influence the toxicity and efficacy of these drugs; however the number of patients evaluated is limited and this has to be considered a pilot study.

[Efficacy of meloxicam in juvenile polyposis syndrome. A case report]. / Poliposi giovanile in un caso clinico in cui e risultata efficace la terapia con meloxicam.

The Authors present a case of a 11 year-old patient with a history of Juvenile Polyposis Syndrome (JPS), a condition characterized by the occurrence of multiple hamartomatous polyps in the gastrointestinal tract. Patients with JPS are traditionally treated by repeated endoscopic polypectomies and elective surgery. Recent studies reported up-regulation of cyclo-ossigenase 2 (COX-2) in colorectal polyps. Specific COX-2 inhibitors have been withdrown from the market for tromboembolic side effects. However efficacy and safety of preferential selective COX-2 inhibitor has been reported as antiinflammatory drugs also in children. In this patient meloxicam treatment, a preferential selective COX-2 inhibitor, leaded to a significant reduction in the number of colorectal polyps during 3 years follow up.

[Interradicular course of the inferior alveolar nerve at the mandibular right third molar and monostotic fibrous dysplasia affecting the mandibular left third molar in the same patient. A case report]. / Interradikulärer Verlauf des N. alveo- laris inferior bei 38 und apikale monostotische fibröse Dysplasie bei 48 beim selben Patienten. Ein Fallbericht.

To minimize the risk of intraoperative complications, a comprehensive radiological diagnostic work-up should be a routine procedure in oral surgery. This is especially true concerning possible damage to the inferior alveolar nerve during surgical removal of the third molars. The course and location of the nerve are best assessed when evaluating panoramic view images or cone beam CTs. The following case report demonstrates and discusses the importance of a thorough radiological evaluation before surgery, the problems raised by an interradicular course of the inferior alveolar nerve, and the finding of a monostotic fibrous dyplasia in the same patient.

Pulp and periodontal healing of laterally luxated permanent teeth: results after 4 years.

AIM: To evaluate the pulp and periodontal healing of laterally luxated permanent teeth. MATERIAL AND METHODS: Patients presenting with lateral luxation of permanent teeth during 2001-2002 were enrolled in this clinical study. Laterally luxated teeth were repositioned and splinted with a TTS/composite resin splint for 4 weeks. Immediate (prophylactic) root-canal treatment was performed in severely luxated teeth with radiographically closed apices. All patients received tetracycline for 10 days. Re-examinations were performed after 1, 2, 3, 6, 12 and 48 months. RESULTS: All 47 laterally luxated permanent teeth that could be followed over the entire study period survived. In 10 teeth (21.3%), a prophylactic root-canal treatment was performed within 2 weeks following injury. The remaining 37 teeth showed the following characteristics at the 4-year re-examination: 19 teeth (51.4%) had pulp survival (no clinical or radiographic signs or symptoms), nine teeth (24.3%) presented with pulp canal calcification, and pulp necrosis was seen in another nine teeth (24.3%), within the first year after trauma. None of the teeth with a radiographically open apex at the time of lateral luxation showed complications. External root resorption was only seen in one tooth. CONCLUSIONS: Laterally luxated permanent teeth with incomplete root formation have a good prognosis, with all teeth surviving in this study. The most frequent complication was pulp necrosis that was only seen in teeth with closed apices.

Exophytic mass of the gingiva as the first manifestation of metastatic pulmonary adenocarcinoma.

BACKGROUND: Metastasis of a malignant tumor to the oral cavity is rare, but it can be the first manifestation of a primary tumor. METHODS: The clinicopathologic features of a gingival metastasis originating from lung adenocarcinoma in a female patient are described. A 57-year-old woman showed a rapidly growing, painless, exophytic mass in the left mandibular gingiva. The whole lesion was excised, and histologic and immunohistochemical analyses were performed. RESULTS: The histopathologic sections showed a proliferation of poorly differentiated spindle and pleomorphic cells. Because the differentiation between carcinoma and sarcoma of spindle cell tumors was difficult, additional immunohistochemical evaluation was performed. The intraoral healing after tumor removal was uneventful. The discrepancy between the histopathologic results and the clinical findings led to a thorough examination by the patient's physician. Finally, a biopsy of the lungs confirmed a poorly differentiated adenocarcinoma with multiple metastases, including the oral cavity. CONCLUSIONS: An exophytic lesion on the gingiva can be the first sign of metastatic adenocarcinoma to the oral mucosa. This case emphasizes that even apparently benign-looking gingival lesions in anamnestically healthy patients need to be examined histopathologically.

Enteral nutrition and microflora in pediatric Crohn's disease.

BACKGROUND: Exclusive enteral nutrition (EN) is an established primary therapy for pediatric Crohn's disease (CD). The mechanism of action of such treatment is still conjectural. The aim of the present study was to investigate if EN-induced remission is associated with modification of the fecal microflora in CD. METHODS: Stool samples were collected from 5 healthy children and adolescents over a period of 3 months, and from 9 children and adolescents with active CD. To induce disease remission, children with CD received a course of exclusive EN for 8 weeks with a polymeric formula (Modulen IBD, Nestlè). At the end of the course of exclusive EN, children returned to a free diet but continued to take 40% of the daily caloric intake as polymeric formula. Fecal microflora was analyzed by 16S ribosomal DNA polymerase chain reaction and temperature gradient gel electrophoresis (TGGE) with direct visual comparison of band profiles of PCR products. RESULTS: In 8 of 9 children, the exclusive EN alone induced disease remission. In 1 child, it was necessary to add steroids to the exclusive EN course to achieve remission. In all children with CD, analysis of gel band distribution revealed profound modification of the fecal microflora after exclusive EN. Variations of band distribution corresponding to different bacterial species were observed also in children on partial EN and required time to achieve stability of the band profile. In contrast, control healthy children showed a host-specific and stable TGGE profile over time. CONCLUSION: These data suggest that a possible mechanism of action of EN in inducing disease remission in CD is the capacity of modification of gut microflora. Possible explanations of such capacity are both low residue and prebiotic properties of the polymeric liquid formula.