ABSTRACT
SIGNIFICANCE: Eosinophilic esophagitis (EoE) is an inflammatory condition characterized by T helper-2 (T H 2) cytokines. Ulcerative colitis (UC) and Crohn disease (CD) are inflammatory conditions with different clinical presentations and immune profiles. UC is associated with T H 2 cytokines and CD with T H 1 cytokines. We investigated potential differences in the association of EoE with UC and CD because of these different immune profiles. METHODS: We utilized ICD-9 and ICD-10 codes to find patients with inflammatory bowel disease (IBD) and EoE. We defined EoE as any esophageal biopsy with >15 eosinophils. We collected demographic, clinical, laboratory, endoscopic, and histological data. RESULTS: Thirty patients had both EoE and IBD. 14.9% of UC patients had EoE and 5.7% of CD patients had EoE. 64.7% of UC patients presented with UC and EoE at the same time, whereas 76.9% of CD patients presented with EoE at follow up. Ten of 13 CD patients were on anti-tumor necrosis factor (TNF) at EoE diagnosis. No UC patients were on anti-TNF at EoE diagnosis. Eighty-three percent of CD patients had mild disease or were in remission, whereas 50% of UC patients had moderate to severe disease at the time of EoE diagnosis. CONCLUSION: A higher percentage of UC than CD patients had EoE. EoE was more likely to be present at the initial diagnosis of UC than CD. EoE was more likely after diagnosis and treatment of CD with anti-TNF, when CD activity was mild or in remission. The difference in presentation suggests that anti-TNF or it's impact on inflammation may differentially impact the association of EoE with CD and UC.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Eosinophilic Esophagitis , Child , Colitis, Ulcerative/complications , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Crohn Disease/complications , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Cytokines , Eosinophilic Esophagitis/complications , Eosinophilic Esophagitis/diagnosis , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnosis , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha/therapeutic useABSTRACT
In these studies, we evaluated the contribution of the NLRP3 inflammasome to Crohn's disease (CD) in a kindred containing individuals having a missense mutation in CARD8, a protein known to inhibit this inflammasome. Whole exome sequencing and PCR studies identified the affected individuals as having a V44I mutation in a single allele of the T60 isoform of CARD8. The serum levels of IL-1ß in the affected individuals were increased compared with those in healthy controls, and their peripheral monocytes produced increased amounts of IL-1ß when stimulated by NLRP3 activators. Immunoblot studies probing the basis of these findings showed that mutated T60 CARD8 failed to downregulate the NLRP3 inflammasome because it did not bind to NLRP3 and inhibit its oligomerization. In addition, these studies showed that mutated T60 CARD8 exerted a dominant-negative effect by its capacity to bind to and form oligomers with unmutated T60 or T48 CARD8 that impeded their binding to NLRP3. Finally, inflammasome activation studies revealed that intact but not mutated CARD8 prevented NLRP3 deubiquitination and serine dephosphorylation. CD due to a CARD8 mutation was not effectively treated by anti-TNF-α, but did respond to IL-1ß inhibitors. Thus, patients with anti-TNF-α-resistant CD may respond to this treatment option.
Subject(s)
CARD Signaling Adaptor Proteins/immunology , Crohn Disease/immunology , Inflammasomes/immunology , Loss of Function Mutation , Monocytes/immunology , Mutation, Missense , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Neoplasm Proteins/immunology , Amino Acid Substitution , CARD Signaling Adaptor Proteins/genetics , Crohn Disease/genetics , Crohn Disease/pathology , Female , HEK293 Cells , Humans , Inflammasomes/genetics , Interleukin-1beta/genetics , Interleukin-1beta/immunology , Male , Monocytes/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Neoplasm Proteins/genetics , Phosphorylation/genetics , Phosphorylation/immunology , Protein Isoforms/genetics , Protein Isoforms/immunology , Ubiquitination/genetics , Ubiquitination/immunology , Whole Genome SequencingSubject(s)
Alopecia Areata/complications , Inflammatory Bowel Diseases/complications , Adolescent , Alopecia Areata/drug therapy , Child , Female , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Methotrexate/adverse effects , Methotrexate/therapeutic use , Prednisolone/adverse effects , Prednisolone/therapeutic useABSTRACT
Information on the utility of solid-phase gastric emptying studies (SPGES) in the evaluation of children with symptoms of upper gastrointestinal (GI) motor dysfunction is limited. This study was conducted to evaluate the impact of SPGES in the clinical management and outcome of children with upper GI symptoms suggestive of gastroparesis. The records of 45 children who underwent SPGES (31F; 3-17 years) were reviewed. All patients had GI symptoms suggesting gastroparesis. Patients were fed with Tc-99m-sulfur colloid-labeled chicken liver. Adult normal half-life (T1/2) values (F 103 +/- 14 minutes; M 66 +/- 13.6 minutes) were used. The relationships among symptoms, treatment, and outcome were evaluated. Of the 45 patients 9 had delayed, 16 had rapid, and 20 had normal gastric emptying. Six of 9 patients with delayed gastric emptying responded to cisapride. Four of 16 patients with rapid emptying were diagnosed with the dumping syndrome. Of the children with rapid gastric emptying, 87% were females. Twenty patients with normal emptying were diagnosed with gastroesophageal reflux (8), nonulcer dyspepsia (5), irritable bowel syndrome (2), Helicobacter pylori (1), lactose intolerance (1), eosinophilic gastroenteritis (1), duodenitis (1), and constipation (1). In patients who had SPGES for possible gastroparesis, 20% had gastroparesis, 36% had rapid gastric emptying, and 44% had normal gastric emptying. The high number of females in the rapid gastric emptying group might be secondary to normal adult female T1/2 values that were used. The practice of using adult normal T1/2 values in prepubertal girls may need to be revised. Patients with delayed gastric emptying responded to cisapride.
Subject(s)
Dyspepsia/therapy , Gastric Emptying , Adolescent , Child , Child, Preschool , Dyspepsia/diagnosis , Female , Humans , MaleABSTRACT
Patients with cystic fibrosis often develop upper gastrointestinal symptoms, which may be due to abnormal gastric motor function. The aim of the study is to determine the characteristics of gastric electrical activity in patients with cystic fibrosis and to compare electrogastrography patterns in symptomatic and asymptomatic patients. Electrogastrography was recorded in 14 symptomatic and 8 asymptomatic children with CF. Both 30-min baseline and 30-min postprandial recordings was obtained. Dominant frequency cycles per minute, rhythm index, and power in decibels were obtained for the fasting and postprandial periods. The percentage of normal gastric waves was not affected by the meal and was significantly low in symptomatic and asymptomatic cystic fibrosis patients. Tachygastria was the most frequent dysrhythmia in both groups. Decreased postprandial power was seen in three symptomatic patients and one patient had no change. The percentage of normal gastric slow waves was low in symptomatic and asymptomatic cystic fibrosis patients. Tachygastria was the most frequent dysrhythmia. Decreased postprandial power was seen only in symptomatic patients.
