A tale of two diseases: the history of inflammatory bowel disease.

'Inflammatory bowel disease' (IBD) sounds like a straightforward term - a disease of inflammation in the bowel. However, the history of IBD reveals a story of a nefariously complex set of idiopathic conditions. IBD defies definition, in part because its pathophysiology is not completely understood. For the same reason and despite substantial advances in research, IBD also defies cure. At best, IBD can be defined as a disease of disruption - disrupted physiology, microbiology, immunology and genetics. The term 'IBD' is most often used to describe two separate conditions: ulcerative colitis (UC) and Crohn's disease (CD). This paper reviews the history of IBD, considering the ever-evolving understanding of both UC and CD. Beyond its intrinsic interest, the history of IBD exemplifies a pattern that is becoming increasingly familiar in the 21st century - the story of a chronic, incurable disease that defies the best efforts to treat it.

Clinical features distinguish eosinophilic and reflux-induced esophagitis.

BACKGROUND AND OBJECTIVES: Diagnosing eosinophilic esophagitis (EoE) depends on intraepithelial eosinophil count of ≥15 eosinophils per high-power field (HPF); however, differentiating EoE from gastroesophageal reflux disease (GERD) continues to be a challenge because no true "criterion standard" criteria exist. Identifying clinical and endoscopic characteristics that distinguish EoE could provide a more comprehensive diagnostic strategy than the present criteria. The aim of the study was to determine symptoms and signs that can be used to distinguish EoE from reflux esophagitis. METHODS: Adult and pediatric patients with EoE were identified by present diagnostic guidelines including an esophageal biopsy finding of ≥15 eosinophils/HPF. Patients with GERD were age-matched one to one with patients with EoE. Clinical, endoscopic, and histologic information at the time of diagnosis was obtained from the medical record and compared between pairs by McNemar test. A conditional logistic regression model was created using 6 distinguishing disease characteristics. This model was used to create a nomogram to differentiate EoE from reflux-induced esophagitis. RESULTS: Patients with EoE were 75% men and 68% had a history of atopy. Many aspects of EoE were statistically distinct from GERD when controlling for age. Male sex, dysphagia, history of food impaction, absence of pain/heartburn, linear furrowing, and white papules were the distinguishing variables used to create the logistic regression model and scoring system based on odds ratios. The area under the curve of the receiver-operator characteristic curve for this model was 0.858. CONCLUSIONS: EoE can be distinguished from GERD using a scoring system of clinical and endoscopic features. Prospective studies will be needed to validate this model.

Risk factors for short- and long-term morbidity in children with esophageal atresia.

OBJECTIVE: To describe short- (first year of age) and long-term (after 1 year of age) outcome in patients with esophageal atresia and identify early predictive factors of morbidity in the first month of life. STUDY DESIGN: Charts of children with esophageal atresia born January 1990 to May 2005 were reviewed. A complicated evolution was defined as the occurrence of at least 1 complication: severe gastroesophageal reflux, esophageal stricture requiring dilatations, recurrent fistula needing surgery, need for gavage feeding for >or=3 months, severe tracheomalacia, chronic respiratory disease, and death. RESULTS: A total of 134 patients were included. Forty-nine percent of patients had a complicated evolution before 1 year of age, and 54% had a complicated evolution after 1 year. With bivariate analysis, predictive variables of a complicated evolution were demonstrated, including twin birth, preoperative tracheal intubation, birth weight <2500 g, long gap atresia, anastomotic leak, postoperative tracheal intubation >or=5 days, and inability to be fed orally by the end of the first month. After 1 year of age, the complicated evolution was only associated with long gap atresia and inability to be fed orally in the first month. A hospital stay >or=30 days was associated with a risk of a complicated evolution at 1 year and after 1 year of age (odds ratio, 9.3 [95% CI, 4.1-20.8] and 3.5 [95% CI, 1.6-7.6], respectively). CONCLUSION: Early factors are predictive of morbidity in children with esophageal atresia.

Design of predictive models for positive outcomes of upper and lower gastrointestinal endoscopies in children and adolescents.

OBJECTIVES: To develop models to accurately determine the outcomes of diagnostic endoscopies performed in children and adolescents without known gastrointestinal disease. MATERIALS AND METHODS: Retrospective chart review of all endoscopies performed in children 2 to 18 years of age without known gastrointestinal disease from January 1 to December 31, 2000. The association between age, presenting symptoms, physical examination findings, laboratory investigations, and endoscopy outcomes was assessed. Predictive models for positive outcomes on endoscopy were estimated for upper and lower endoscopies separately by use of multiple logistic regression. Receiver operating curves were constructed to evaluate the performance of the models. A model with a sensitivity of 95% and specificity of 40% was considered clinically significant. RESULTS: Positive findings on endoscopy were found in 191 (55%) of 346 and in 120 (59%) of 204 upper and lower endoscopies, respectively. Age above 13 years, vomiting, and hypoalbuminemia were significant predictors of positive upper endoscopies. Rectal bleeding, hypoalbuminemia, and elevated erythrocyte sedimentation rate were significant predictors of positive lower endoscopies. Extrapolating from the receiver operating curves, a sensitivity of 95% corresponded to a specificity of 10% for the upper endoscopy model and 30% for the lower endoscopy model. CONCLUSIONS: In our population of children and adolescents, several clinical characteristics were predictive of positive upper and lower endoscopy outcomes. Predictive models composed of these clinical variables were statistically, but not clinically, significant. The inclusion of additional clinical characteristics that could be assessed in prospective studies will likely improve the clinical significance of endoscopy outcome prediction.

Increased dosing requirements for 6-mercaptopurine and azathioprine in inflammatory bowel disease patients six years and younger.

BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are effective for the induction and maintenance of remission and reduction of corticosteroid exposure for pediatric inflammatory bowel disease (IBD). The standard dose of 6-MP is 1.0-1.5 mg/kg/day and for AZA is 2.0-2.5 mg/kg/day. The aim of this study was to determine whether IBD patients 6 years of age and younger require higher than standard doses of 6-MP/AZA to achieve clinical remission. METHODS: Clinical data was collected retrospectively for all IBD patients 6 years of age or younger treated with 6-MP/AZA at The Children's Hospital of Philadelphia. RESULTS: Thirty patients met the inclusion criteria. IBD was diagnosed at a median age of 3.3 years (25-75th %ile 2.3-4.6 years) and 6-MP/AZA was initiated at a median age of 3.9 years (range 0.8-6.8 years). After dose escalation, the median AZA-equivalent dose was 3.1 mg/kg/day (25-75th %ile 2.5-3.5, max. dose 5.1 mg/kg/day). At the final recorded dose, 8/13 (62%) patients receiving AZA >3.0 mg/kg/day achieved clinical remission, compared to 2/12 (17%) receiving 2-3 mg/kg/day (P = 0.02). The risk of having active disease was on average 85% lower if the AZA-equivalent dose was >3.0 mg/kg/day (95% confidence interval [CI] 72%-93%). Adverse events were experienced by 4/30 patients (hepatitis, n = 2; leukopenia, n = 2). No patients had to discontinue 6-MP/AZA, and all laboratory abnormalities improved spontaneously or with dose reduction. CONCLUSIONS: The standard dose of 6-MP/AZA may not be adequate for IBD patients 6 years of age and younger. Closely monitored dose escalation beyond the standard dosing range is effective and well-tolerated.