Allergic Colitis Research Articles

Azines as histamine H4 receptor antagonists

Since 2000, when the histamine H4 receptor (H4R) was cloned, it has constituted an interesting target for drug development. Pharmacological studies suggest the potential utility of histamine H4R antagonists/inverse agonists in the treatment of inflammatory diseases, e.g. allergic rhinitis, asthma, atopic dermatitis, colitis, or pruritus. The first H4R ligands were non-selective compounds, but intensive chemical and pharmacological work has led to the discovery of highly potent and selective H4R antagonists (e.g. JNJ7777120, CZC-13788, PF-2988403, A-940894, A-987306). The first compound (UR-63325) has finally entered into clinical studies for the treatment of allergic respiratory diseases (completing the phase I ascending dose trial) and has been found to be safe and well tolerated. The number of scientific publications and patent applications in the H4 field is increasing annually. Among the diverse chemical structures of the H4R antagonists described a 2-aminopyrimidine scaffold is repeatedly found. This review looked at recent advances in the search for H4R antagonists as reflected in patent applications/patents and peer-reviewed publications over the last two years. The work concerns azines (mono-, di-, triazines) and their fused analogues. The chemistry and pharmacology has been described.

Non-IBD colitides: clinically useful histopathological clues

Apart from inflammatory bowel diseases (IBD), there are several other form of colitis that may resemble macroscopically IBD, entering the differential diagnosis. These forms are represented by infectious colitis, ischemic colitis, pseudomembranous colitis, colitis related to diverticular disease, colitis related to mucosal prolapse, drug colitis, allergic colitis, and microscopic colitis. However, to distinguish between these forms is not always easy, and it frequently requires a strict interrelationship between the pathologist and the gastroenterologist. Here we discuss the more frequent forms of non- inflammatory bowel diseases colitides, trying to give useful hints for helping the clinician to better understand the extent to which the pathologist is called to give a definitive response in the differential diagnosis of these entities.

Response to Drs Gordon and Clark

We appreciate the interest shown in our case report and the comments of Drs Gordon and Clark.1 Gordon and Clark provide very interesting findings from the largest dataset of preterm infants with necrotizing enterocolitis (NEC) and their eosinophil counts at the time of the NEC diagnosis. In their dataset, in addition to the lack of feeding history (pathogenesis of allergic colitis is driven by dietary antigens), it is not clear whether stool examination for leucocytes was done in the subset of NEC patients categorized based on peripheral eosinophil count. The supposition about the allergic enterocolitis as a benign entity compared to NEC in general is based on lack of reported mortality rates in neonatal literature attributed to allergic enterocolitis as a clinical entity in itself and the dramatic improvement and non-progression of systemic symptomatology with removal of offending dietary antigen. Although a mortality rate of 16.8% relative to the higher mortality rate of 22% between low (<10) eosinophil count and higher eosinophil count (10) groups with NEC may appear important, for a condition thought to be benign, even 16.8% mortality may be considered high by many in neonatal practice, if this subset were to truly represent allergic enterocolitis.

Regulatory T Cells and T Helper Subsets in Breast‐fed Infants With Hematochezia Caused by Allergic Colitis

The objective of our study was to investigate the prevalence of CD4 T lymphocyte subsets and their commitment to TH1 or TH2 direction in 10 infants with allergic colitis (AC) and 10 healthy controls. Infants with AC presented with a higher ratio of naïve to memory cells, lower prevalence of activated CD4CD25 cells and FoxP3 regulatory cells, and a shift to TH2 direction in balance compared with controls. These alterations are normalized upon cessation of AC symptoms on elemental L-amino acid formula. These findings suggest the importance of antigen exposure in AC in infancy.

1066 A Pilot Trial on Acceptability, Tolerance, and Efficacy of a Thickened Extensive Casein Hydrolysate (Allernova ARâ)

Rationale: Regurgitation and irritability are common in infants, and occur as manifestation of GER and cow milk allergy (CMA). Thickened formula is effective in (troublesome) regurgitation and mild GERD, and an extensive hydrolysate is recommended in CMA. Methods: A prospective, open trial was conducted to evaluate the efficacy of an extensive caseinhydrolysate thickened with specifically treated starch in 24 infants with a suspected diagnosis of mild GERD and/or gastro-intestinal manifestations of CMA (all infants regurgitated or vomited > 4 times/day). Previous interventions (at least one dietary change and one drug for GERD) had failed in all infants. Results. 6/24 infants (25 %) dropped out because of pyloric stenosis (n:1), urinary tract infection (n:1), severe combined immune deficiency (n:1), no improvement of symptoms (crying and vomiting) (n:3). The formula was well tolerated in 18/24 infants, and administered up to the age of 6 months. In total, “Allernova-AR” was consumed during 2165 trial-days. Objective arguments for CMA were observed in 8/18 infants (eosinophilia (n:3), allergic colitis (n:2), partial atrophy villi (n:2); positive skin prick test (n:2)). The mean duration of feeding was 125 days. Weight and length evolution were normal. Regurgitation at baseline (mean 5.85) decreased after one week by more than 50 % (mean 2.12)(p:< 0.001). The Infant-GER-Questionnaire showed a clinical meaningful improvement of at least 5 points in all 18 infants tolerating the new formula. Conclusion: Given the frequent simultaneous occurrence in infants of symptoms suggesting CMPA and/or GERD, Allernova-AR provides practitioners an effective and safe therapeutic option.

Probiotics in the management of children with allergy and other disorders of intestinal inflammation

Soon after birth, the human gastrointestinal tract quickly becomes colonised by a variety of bacterial species. Throughout life the gastrointestinal tract continues to serve as host to a complex society of nonpathological bacteria. Microorganisms, such as probiotics, have the potential to modulate mucosal immune response and reduce gastrointestinal inflammation caused by a variety of infectious and allergic events. The most widely studied genera of probiotics are lactobacilli and bifidobacteria. Lactobacillus rhamnosis strain ATC53103 (LGG) can replenish gut flora during infectious diarrhoeal episodes. This beneficial effect is carried over to traveller's diarrhoea and children experiencing antibiotic-associated diarrhoea. Furthermore, LGG can reduce the risk of respiratory tract infections in children attending daycares and hospitals. With allergic disease on the rise, probiotics have the potential to positively impact atopic dermatitis, asthma, and allergic rhinitis. LGG has been shown to decrease the severity and delay the onset of atopic dermatitis. Additionally, LGG is beneficial in the treatment of allergic colitis and necrotising entercolitis. Some strains of probiotics appear to be useful in the treatment and/or prevention of allergic disease, however, caution must be used when generalising the effectiveness of a specific strain of organism to other organisms and other disease states.

Probiotics for Cow's Milk Protein Allergy in Infants

Cow's milk-protein allergy is relatively common in both formula-fed and breast-fed infants and can cause colitis that is characterized by rectal bleeding and often loose stools with or without mucus. Cow's milk allergic colitis (CMAC) is usually diagnosed presumptively (instead of by biopsy) and is treated by changing to an extensively hydrolyzed casein formula (EHCF) or by eliminating dairy in the mother's diet …

Lactobacillus GG Improves Recovery in Infants with Blood in the Stools and Presumptive Allergic Colitis Compared with Extensively Hydrolyzed Formula Alone

To determine the benefits of Lactobacillus rhamnosus GG (LGG) in an extensively hydrolyzed casein formula (EHCF) in improving hematochezia and fecal calprotectin over EHCF alone. Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group. We also compared fecal calprotectin and hematochezia on 26 formula-fed infants randomly assigned to EHCF with LGG (Nutramigen LGG) (EHCF + LGG) or without (Nutramigen) (EHCF - LGG) and on 4 breastfed infants whose mothers eliminated dairy. Fecal calprotectin in those with hematochezia was significantly higher than in comparisons (mean +/- SD 325.89 +/- 152.31 vs 131.97 +/- 37.98 microg/g stool, t = 6.79, P < .0001). At 4 weeks, fecal calprotectin decreased to 50% of baseline but was still significantly higher than in comparisons (157.5 +/- 149.13 vs 93.72 +/- 36.65 microg/g, P = .03). Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG (-214.5 +/- 107.93 vs -112.7 +/- 105.27 microg/g, t = 2.43, P = .02). At 4 weeks, none of the EHCF + LGG had blood in stools, and 5/14 on EHCF - LGG did (P = .002). Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis. EHCF + LGG resulted in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone.

Food Protein-Induced Enterocolitis Syndrome: 16-Year Experience

Mehr S, Kakakios A, Frith K, Kemp AS. Pediatrics. 2009;123(3). Available at: www.pediatrics.org/cgi/content/full/123/3/e459 PURPOSE OF THE STUDY. To investigate possible patterns in demographic features, causative foods, clinical features, treatments at presentation, and outcomes in children diagnosed with food protein-induced enterocolitis syndrome (FPIES). STUDY POPULATION. Retrospective chart review of 35 children who presented with acute FPIES at a tertiary medical center in New South Wales, Australia, between 1992 and 2007. METHODS. Diagnosis was made by pediatric allergists after referral to the allergy clinic (74%) or from the emergency department (ED) (26%), using previously published criteria. Cases were identified by codes signifying allergic and dietetic gastroenteritis and colitis or by …

Serologic investigations in children with inflammatory bowel disease and food allergy.

The aim of the study was the evaluation of frequency and titre of IgA ASCA and IgG ASCA and p-ANCA, c-ANCA in children with IBD and occurrence of ASCA antibodies in relation to coexistence of FA. Patients and methods. The study comprised 95 children at the ages of 2 to 18 years. The diagnosis of IBD was established on the basis of Porto criteria. Tests of blood serum were performed in all children: IgA and IgG ASCA, p-ANCA, c-ANCA using ELISA method. Results. IgE-dependent FA was found in 32.5% children with UC and in 21% with CD. We did not observe any relation between the occurrence of FA and the frequency and ASCA titre. p-ANCA were significantly more frequent in the group of children with UC. The occurrence of ASCA antibodies was observed in 73.7% of children with CD, 17.5% with UC and almost 30% with allergic colitis. Conclusions. Patients with CD and the presence of ASCA revealed a significantly more frequent localization of lesions within the small bowel and a tendency towards older age. We observed a connection between the occurrence of antibodies and the examined mutations of gene NOD2/CARD15.

Does inflammatory bowel disease develop in infants?

Does inflammatory bowel disease develop in infants?

Primary CMV Colitis in an Immunocompetent Infant, Successfully Treated by Gancyclovir

Primary CMV Colitis in an Immunocompetent Infant, Successfully Treated by Gancyclovir

IBD and IBD mimicking enterocolitis in children younger than 2 years of age

Inflammatory bowel disease (IBD) is uncommon in children younger than 2 years of age. The criteria for differentiating IBD from other diseases with similar clinical presentation is unclear. We describe 16 patients who, between 1984 and 2004, received a histological diagnosis of IBD during the first two years of life. Six patients presented with histological Crohn's disease, eight with ulcerative colitis and two with indeterminate colitis. The median age at diagnosis was 125 days (range 1 day to 18 months) and the medium follow up was 89 months (range 65 days to 20 years). The disease appeared to be very severe: four children (25%) underwent total parenteral nutrition (TPN), two received colectomy (12.5%) and three patients died. Many of the patients required an aggressive, multidrug, immunosuppressive approach (azathioprine [AZA], Infliximab, thalidomide, cyclosporine A). One child presented with a hypogammaglobulinaemia without any specific immunodeficiency, while in the other patients, Wiskott-Aldrich syndrome (WAS) (4 cases) and chronic granulomatous disease (CGD) (2 cases) were identified. In 6/16 cases, allergic colitis was first considered; these cases initially underwent cow's milk protein-free diet as the only therapy before IBD was finally diagnosed. In conclusion, early IBD has a severe prognosis and often needs an aggressive therapeutic approach. Furthermore, an improper diagnosis of allergic colitis might cause an important diagnostic delay. Some severe immunodeficiencies, such as WAS and CGD, may represent a problem in terms of differential diagnosis and might be wrongly diagnosed as very early onset IBD.

Comparison of intestinal microflora in healthy infants and infants with allergic colitis

Twenty-eight exclusively breast-fed healthy infants and 16 infants also exclusively breast-fed with allergic colitis (aged 85 +/- 60 and 98 +/- 58 d, respectively) were screened for differences in fecal flora. Bifidobacteria were detected in 23 healthy infants and only in 4 fecal samples of infants with allergic colitis. All bifidobacteria-free infants possessed Gram-positive regular rods as a major group of their fecal flora. These bacteria were identified as clostridia using genus-specific FISH probe. Infants with allergy colitis possessed significantly lower counts of bifidobacteria and total anaerobes and significantly higher counts of clostridia in their feces. In healthy infants, Bifidobacterium longum was the most frequently found species (54.5% of the samples), followed by B. adolescentis (20.0), B. breve (18.2), B. bifidum (16.4), B. dentium (10.9) and B. pseudocatenulatum (1.80). Bifidobacterial isolates from two babies with allergic colitis were identified as B. longum, one child from patients group contained species B. dentium and one baby B. adolescentis. Our results suggest that there are significantly lower counts of bifidobacteria in infants with allergic colitis than in healthy infants.

Optimal Treatment of Campylobacter Dysentery

A 9 day old Caucasian female infant was admitted to a general pediatric floor from an outside hospital for a 23 hour observation and treatment of dehydration associated with severe diarrhea. Parents reported frequent stools for 4 days prior to admission with possible hematochezia 1 day prior to admission. Stools were occurring every 15 to 20 minutes at times. No vomiting or fever accompanied the diarrheal episodes. The child’s formula was changed 3 days prior to admission with no improvement in symptoms. Her birth history included an uncomplicated vaginal delivery at 38 weeks, with a birth weight of 2.93 kg. No medical problems or abnormalities had been identified prior to this hospital admission. She had no previous contact with sick individuals or exposure to pets. The patient’s mother has alpha I antitrypsin deficiency, but no other pertinent family history was identified. On admission, the patient weighed 2.77 kg and the physical exam revealed soft and flat fontanelles, and pink, wet oral mucosa. Bowel sounds were present throughout and the abdomen was soft and non-distended. Stools were sent to the lab for culture and sensitivity. The

Inhibition of Graft-Versus-Host-Disease (GVHD) by Treatment with the Cyclopentenone Prostaglandin 15d-PGJ2 Involves Modulation of the NF-κB Signaling Pathway.

Graft-versus-host disease (GVHD) mediated by alloreactive donor T cells is the most dreaded complication after allogeneic bone marrow transplantation (BMT). Interaction of donor T cells with host antigen presenting cells is considered to be central to the development of GVHD. Furthermore, GVHD development depends on the inflammatory response induced by the conditioning regimen. Interfering with inflammatory signaling pathways could be an approach to prevent GVHD without compromising the graft-versus-malignancy reaction. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor transcription factor that regulates cell growth, differentiation and homeostasis. PPARγ agonists, such as 15-deoxy -Δ12,14-Prostaglandin J2 (15d-PGJ2) have been shown to have potent immunomodulatory effects on B and T lymphocytes as well as DCs, and recent studies have demonstrated protective effects of PPARγ agonists on animal models of autoimmunity including experimental allergic encephalomyelitis (EAE), asthma, arthritis, colitis and diabetes. There is very few data addressing the role of PPARγ agonists on GVHD. The aim of this study was to investigate the protective effect and mechanism of 15d-PGJ2 on experimental GVHD. GVHD was induced following lethal irradiation (1075 rad) using the fully MHC-mismatched strain combination BALB/c to B6. Recipients were treated with 1 mg/kg of 15d-PGJ2 i.p on days −1, +1, +3, +5 and +7 post-BMT. Treatment with 15d-PGJ2 resulted in a significantly reduced GVHD mortality (p=0.01 log rank test) with a Median Survival Time (MST) of 23 days in the control group. Median survival was not reached in the 15d-PGJ2 treatment group at the end of the observation period (day +50 post BMT). Furthermore, we found a significant reduction in donor T cell expansion of 15d-PGJ2-treated animals on day +6 post-BMT. To further delineate the mechanisms underlying its protective effect, we analyzed the effects of 15d-PGJ2 on alloantigen-driven proliferation in MLR cultures in vitro as well as development and maturation of mouse bone marrow derived- dendritic cells (DC) in vitro. Treatment with 15d-PGJ2 resulted in a dose-dependent inhibition of allo-antigen driven proliferation. Furthermore, using a 12-day culture system 15d-PGJ2 led to a significant reduction of mature DC as determined by the number of DC co-expressing CD40, CD80, CD86. Treatment for 24 hours with 5uM of 15d-PGJ2 significantly inhibited activation of the NF-κB pathway as demonstrated by abrogation of p65 and IkB-α phosphorylation in response to alloactivation and also in 15d-PGJ2 treated DC using western blot analysis. In conclusion our data support the notion that the inhibitory effect of 15d-PGJ2 on the development of GVHD involves NF-κB-dependent inhibition of DC maturation and expansion of donor T cells. Given its potent antitumor effects cyclopentenone prostaglandins could be ideal candidates for prevention of GVHD while maintaining Graft versus malignancy effects.

Pediatric Jejunal Gastrointestinal Stromal Tumor Diagnosed by Wireless Capsule Endoscopy

Pediatric Jejunal Gastrointestinal Stromal Tumor Diagnosed by Wireless Capsule Endoscopy

Allergic colitis in infants: Preliminary results of sigenp prospective study

re likely to be more susceptible to these problems due to possible disturances of both oesophageal function and respiratory regulation at this stage f life. In our cases almost all GER-related apnoeas were linked with noncid GER (63/64). pH-monitoring alone does not recognize these episodes f GER. This highlights the importance of combined pH-MII monitoring o characterize all GER features. Furthermore 20 apnoeas were related to GER that is possible recognize only by a manual analyse of the impedance egistration. Most apnoeas are preceded by reflux (48/64): this finding suports our hypothesis that GER is the causative factor. Seventeen percent of pnoeas was related to swallow events; further studies are necessary in order o clarify the relationship between these two events.

Rectal bleeding in Egyptian children

In a prospective study to outline the aetiology of bleeding per rectum (BPR) in Egyptian infants and children, a subsidiary aim was to define some of the clinical characteristics of the different aetiologies. 194 children with BPR are described. The diagnostic work-up included laboratory investigations, radiological and endoscopic assessment, radio-isotope scanning, angiography and histopathological examination of mucosal biopsies, as appropriate. Ages ranged from 3 to 192 months with a mean (SD) of 49.8 (43.5). Infectious enterocolitis was the most common cause (37.1%). Others included colorectal polyps (21.1%), chronic colitis (16%) including inflammatory bowel diseases (5.2%), allergic colitis (2.6%), solitary rectal ulcer syndrome (1.5%) and non-specific colitis (6.7%). Intussusception and Meckel's diverticulae were the cause in 7.3% and 2.6%, respectively, while other aetiologies included vascular (6.2%), systemic (3.6%), local anal (3.1%) and upper gastro-intestinal causes (1.5%). In 1.5% of cases, the cause remained 'obscure'. In Egyptian children, infectious enterocolitis followed by colorectal polyps and chronic colitis are major causes of BPR.

Prevalence and Outcome of Allergic Colitis in Healthy Infants With Rectal Bleeding: A Prospective Cohort Study

Purpose of the Study. To determine the prevalence of allergic colitis (AC) in a cohort of healthy infants with rectal bleeding. A secondary purpose was to determine if bleeding would resolve in untreated infants with rectal bleeding without biopsy-proven AC. Study Population. There were 22 infants ≤6 months of age with rectal bleeding recruited from the referral area of Cincinnati Children’s Hospital Medical Center (Cincinnati, OH). All subjects had a negative history of bleeding disorders, negative stool cultures, positive hemoccult, and a negative history and physical examination for signs of infection, Hirschsprung disease, and inflammatory bowel disease. Methods. AC was defined histologically as colonic mucosa with ≥6 eosinophils per high-power field and/or eosinophils in the colonic crypts or muscularis mucosae. Formula or maternal diet was changed only for infants with histologic findings of AC. Formula-fed infants were switched to an extensively hydrolyzed formula and were rebiopsied at 3 weeks. If the biopsy was normal, they were continued on the formula and managed clinically. Those with continued histologic evidence of colitis were changed to an amino acid–based formula and rebiopsied at 6 weeks. Breastfed infants continued breastfeeding while mothers followed a milk-protein–free diet. Those with resolution of bleeding and normal biopsies at 3 weeks continued with breastfeeding and a restricted maternal diet. Those with persistent histologic evidence of colitis were rebiopsied at 6 weeks with no further dietary change. Those with persistent bleeding were changed to hydrolysate and rebiopsied at 6 weeks. Those with persistent bleeding and histologic evidence of AC at 6 weeks were changed to an amino acid–based formula. Results. Of 22 subjects, 14 (63.6%) had histologic evidence of AC. Five had normal biopsies and 3 had nonspecific colitis. Seven of the 14 with AC were formula fed. Six of the 7 had resolution of bleeding, on average, in 1.8 weeks (range: 1–5 weeks). One of the 7 was changed to an amino acid formula at 3 weeks and had resolution of bleeding at 5 weeks. The remainder of the 14 were breastfed. Six were followed to completion of the study. One had a delayed diagnoses because of development of worsening rectal bleeding and an abnormal biopsy at week 3 despite a normal biopsy at the onset of the study. The infant failed to improve with hydrolyzed formula but had resolution of bleeding by week 8 after initiation of an amino acid formula. Of the remaining 5, 2 had normal histology at week 3 with maternal elimination of cow’s milk. Two had improvement by week 3, and 1 had no change. The average time for resolution in the breastfed group was 5.6 weeks (range: 2–8 weeks). For the 5 infants without histologic evidence of colitis, the average time for resolution of bleeding was 3.25 weeks. In those with nonspecific colitis, 2 had resolution by week 6, and the third was ultimately diagnosed with inflammatory bowel disease. Conclusions. A significant proportion of infants with rectal bleeding may not have AC and may undergo unnecessary, expensive formula or maternal diet changes that may discourage breastfeeding. Reviewer Comments. This small study provides important insights about the prevalence and natural course of proctocolitis. A much larger prospective placebo-controlled study that compares treatment versus no treatment would be very helpful.