Eunice Trindade

Omalizumab in the treatment of eosinophilic esophagitis and food allergy

Omalizumab is currently used in severe asthma and has been tried in other allergic disorders. The authors report two patients with multiple food allergies and eosinophilic esophagitis on a very restrictive diet who have been treated with omalizumab, in order to improve food intolerance—the major distressing factor in their lives. The patients significantly improved in the reported symptoms. However, no improvement was seen regarding esophageal endoscopy and histology. Given the poor histological and endoscopy response, eosinophilic esophagitis persistence is unlikely to be IgE dependent. Omalizumab may improve the quality of life of patients with severe food allergy by improving symptoms, but it does not appear to change endoscopic and histological features of eosinophilic esophagitis in a short follow-up.

Delayed gastric emptying and gastroesophageal reflux: a pathophysiologic relationship.

Background Delayed gastric emptying (DGE) is frequent in patients with gastroesophageal reflux (GER), but its pathophysiologic role has not yet been established. To identify a relationship between DGE and GER, we assessed whether DGE increases esophageal acid exposure and the related importance of possible mechanisms. Methods Thirty pediatric patients with pathological GER were divided according to gastric emptying scintigraphy into a DGE group (n = 14) and normal-emptying group (n = 16). The esophageal pH-monitoring parameters of the two groups were compared with respect to the individual variation between postprandial and fasting periods. Results Patients with DGE had less total acid exposure than did those with normal emptying, but patients in both groups had a pathological fraction of time when pH was below 4 in both the postprandial (median: 18 vs. 27.6;P = 0.49) and fasting (8.5 vs. 23.9;P = 0.01) periods. Patients in the normal-emptying group had similar fraction of time when pH was below 4 in the postprandial and fasting periods. However, patients in the group with DGE had a fraction of time when pH was below 4 in the postprandial period that was almost double that presented in fasting period (postprandial to fasting ratio: 2.11:0.90;P = 0.002). The postprandial to fasting ratio for episodes per hour was similar in the two groups (1.81 vs. 1.79;P = 0.62). Patients with DGE had a significantly higher frequency of long episodes in the postprandial period than did those with normal emptying (62.5% vs. 38.2%;P = 0.04). The occurrence of the longest episode in the postprandial period was also significantly higher for patients with DGE (57.1% vs. 6.2%;P = 0.003). Conclusions DGE seems to accentuate postprandial reflux by increasing the volume of refluxate per episode of reflux through an underlying incompetent lower esophageal sphincter.

NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease

Background: NOD2/CARD15 was described as the first susceptibility gene to Crohns disease (CD). Polymorphisms in the TNFA gene and in the IL1 gene cluster, which are associated with an enhanced chronic inflammatory response, may also play a role in the development of CD. The aim of this study was to determine the association of polymorphisms in the CARD15, TNFA, IL1B, and IL1RN genes with risk of development of CD and with the clinicopathological profile of CD patients. Methods: In a case‐control study including 235 CD patients and 312 controls (929 controls for TNFA genotyping), the CARD15 (R702W, G908R, and1007fs), TNFA (−308G/A and −857C/T), IL1B (−511C/T), and IL1RN (intron 2 variable number of tandem repeats) polymorphisms were genotyped. Results: We observed a significant association between CD and the CARD15 polymorphisms, with an odds ratio (OR) of 2.9 [95% confidence interval (CI), 1.9 to 4.6] for carriers of 1 variant allele and an OR of 11.8 (95% CI, 3.5 to 40.4) for carriers of 2 variant alleles. Patients with CARD15 polymorphisms had more frequently ileal or ileocolonic disease location, stricturing phenotype, abdominal surgery, and no extraintestinal manifestations. The TNFA‐308A/A genotype was associated with susceptibility to CD with an OR of 3.0 (95% CI, 1.2 to 7.2). TNFA‐308A/A homozygotes showed a higher frequency of erythema nodosum and arthritis, colonic disease location, and absence of abdominal surgery. No associations were found with the TNFA‐857, IL1B‐511, and the IL1RN VNTR polymorphisms. Conclusions: These findings suggest that CARD15 and TNFA‐308 genetic polymorphisms are associated with increased risk of CD displaying distinct clinicopathological profiles.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

Background:The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods:A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006–2011. Results:We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0–14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein–Barr virus–associated lymphomas. Conclusions:Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Celiac disease in first degree relatives of celiac children

CONTEXT The first degree relatives of celiac patients represent a high risk group for the development of this disorder, so their screening may be crucial in the prevention of long-term complications. OBJECTIVE In order to determine the prevalence of celiac disease in a group of first degree relatives of children with proven gluten intolerance, we conducted a prospective study that consisted in the screening of celiac disease, using a capillary immunoassay rapid test that allows a qualitative detection of IgA antibody to human recombinant tissue transglutaminase (IgA-TTG). METHODS When the screening test was positive subjects were advised to proceed with further investigation. The screening test was performed in 268 first degree relatives (143 mothers, 89 fathers, 36 siblings) corresponding to 163 children with celiac disease. RESULTS Screening test was positive in 12 relatives (4.5%), of which 1 refused to continue the investigation. In the remaining 11 relatives celiac disease was diagnosed in 7 cases (2.6%, 5 mothers, 2 fathers) who had a median age of 39 years (27-56 years), mild gastrointestinal symptoms, high titre of IgA-TTG and histology abnormalities confirming the diagnosis. All these patients are currently on a gluten-free diet. CONCLUSION The prevalence of celiac disease among first degree relatives (2.6%) was 5 times higher than that in the general population. Although the recommendations for screening asymptomatic high risk groups, such as first degree relatives, are not unanimous the early diagnosis is crucial in preventing complications, including nutritional deficiency and cancer.

Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child.

Invasive Haemophilus influenzae type b (Hib) disease decreased dramatically after the introduction of conjugate vaccine in routine immunization schedules. We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinskis sign was positive. The cerebrospinal fluid (CSF) analysis showed pleocytosis and high protein level. Empiric intravenous antibiotics (ceftriaxone and vancomycin) were administered for suspected bacterial meningitis during 10 days. Serotyping of the Haemophilus influenzae strain found in CSF revealed a serotype b. After one year of follow-up no Hib meningitis sequelae were noted. Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure. Efforts to keep the low incidence of invasive Hib disease should be directed to the maintenance of high vaccination coverage rates, combined with the notification and surveillance strategies already implemented in each country.

A Systematic Review and Meta-Analysis of 6-Thioguanine Nucleotide Levels and Clinical Remission in Inflammatory Bowel Disease

Background and Aims Thiopurines are widely used in the management of inflammatory bowel diseases. However, their minimum effective dose and dose-response relationship remain undefined, and evidence about their use in clinical practice is mostly heterogeneous. This systematic review and meta-analysis aimed: i] to assess the clinical value of 6-thioguanine nucleotide thresholds; and ii] to compare mean 6-thioguanine nucleotide concentrations between patients in clinical remission vs. those with active disease. Methods A systematic literature search was carried out using four databases. Statistical heterogeneity was assessed with the I2 statistic followed by subgroup and sensitivity analyses. Odds ratios were computed using the random-effects model. Results A total of 1384 records were identified in the systematic search, of which 25 were retained for further analysis: 22 were used in the cut-off comparisons and 12 were used in the 6-thioguanine nucleotide mean differences analysis. The global odds ratio for remission in patients with 6-thioguanine nucleotide levels above the predefined thresholds was 3.95 (95% confidence interval [CI], 2.63-5.94; p < 0.001]. When considering the different thresholds individually, the odd ratios were significant for values above 235 pmol/8 × 108 and 250 pmol/8 × 108 red blood cells [2.25 and 4.71, respectively]. Mean 6-thioguanine nucleotide levels were higher among patients in clinical remission, with a pooled difference of 63.37 pmol/8 × 108 red blood cells [95% CI, 31.81-94.93; p < 0.001]. Conclusions This study reinforces the link between 6-thioguanine nucleotide levels and clinical remission in inflammatory bowel diseases, also exploring the validity of specific 6-thioguanine nucleotide thresholds to predict clinical outcomes.

Endoscopic Mucosectomy in a Child Presenting with Gastric Heterotopia of the Rectum

Gastric mucosal heterotopia has been described in all levels of the gastrointestinal tract. Its occurrence in the rectum is uncommon. We report the case of a 4-year-old boy referred to Pediatric Gastroenterology for intermittent rectal bleeding for the past 2 years. Total ileocolonoscopy revealed a flat, well-circumscribed lesion of 4 cm, with elevated margins, localized at 10 cm from the anal verge. Histologic examination showed typical gastric mucosa of the oxyntic type. Treatment with proton pump inhibitors was started without resolution of the symptoms and, therefore, an endoscopic mucosal resection was performed. Heterotopic gastric mucosa represents a rare cause of rectal bleeding in children and endoscopic evaluation is fundamental for diagnosis. Although not usually performed in pediatric ages, endoscopic mucosectomy allows complete resolution of the problem avoiding surgery.

Vulvar inflammation: a presentation of Crohn's disease

An otherwise healthy 13-year-old girl presented with a 6-week history of painless vulvar swelling and erythema which was previously treated with topical corticosteroids and antifungals without improvement. There was no history of trauma or sexual abuse, and the physical examination revealed an asymmetric vulvar swelling and erythema of the right labia (figure 1). Laboratory work-up was normal, except for a raised faecal calprotectin level of 628 µg/g …

Refractory monogenic Crohn’s disease due to X-linked inhibitor of apoptosis deficiency

Dear Editor: Crohn’s disease (CD) is an idiopathic, chronic inflammatory process that can affect any part of the gastrointestinal tract. Susceptibility to disease is influenced by a complex interplay of genetic and environmental factors. Most of the genes thought to be involved in the development of the disease play a role in mucosal immunity, and their products are found on the mucosal barrier epithelium. X-linked inhibitor of apoptosis (XIAP) deficiency (also known as X-linked lymphoproliferative syndrome type 2, XLP-2) is a rare primary immunodeficiency. Since the disease was clarified as a unique entity in 2006, more than 70 cases have been reported. The main clinical features of XLP-2 are elevated susceptibility to hemophagocytic lymphohistiocytosis, recurrent splenomegaly, and inflammatory bowel disease (IBD) with the characteristics of CD [1]. The first description of severe CD in XIAP-deficiency was published in 2011 [2]. Today, XIAP variants in male patients with pediatric-onset CD represent about 4 % of patients and are characterized by refractoriness to several treatments [3]. The clinical spectrum of the 27 patients with XIAP deficiency was recently reported [1]. Seven of these patients developed severe IBD resembling CD with clinical findings of granulomatous inflammation, recurrent colonic strictures, severe perianal fistulas, as well as, pancolitis and ulcerations affecting stomach and small bowel [1]. Herein, we describe a patient with XIAP-deficiency with disease onset at 13 years of age with a severe CD-like illness, refractory to several medical and surgical treatments. A 13-year-old male patient complained of a scrotum abscess without any other symptoms. The past medical history showed a normal length and weight development, infectious mononucleosis, viral meningitis, and Henoch-Schonlein purpura at 3, 6, and 8 years of age, respectively. He had no family history of IBD. A presumptive diagnosis of a CD was made at 13 years of age with Montreal classification A1L2B1p. The patient began therapy with azathioprine (2.0 mg/kg/day). Despite the treatment, 2 years later, he started to complain Int J Colorectal Dis (2016) 31:1235–1236 DOI 10.1007/s00384-015-2442-0