Early life factors are associated with risk for eosinophilic esophagitis diagnosed in adulthood.

Early life exposures have been associated with pediatric eosinophilic esophagitis (EoE), but it is unknown if a similar association is present in adults. We aimed to assess the association between early life risk factors and development of EoE in adulthood. To do this, we conducted a case-control study which was nested within a prospective cohort study of adults undergoing outpatient endoscopy. Cases of EoE were diagnosed per consensus guidelines; controls did not meet these criteria. Subjects and their mothers were contacted to collect information on four key early life exposures: antibiotics taken during the first year of life, Cesarean delivery, preterm delivery (≤37 weeks' gestation), and neonatal intensive care unit (NICU) admission. We calculated the odds of EoE given in each exposure and assessed agreement between subjects and their mothers. For the 40 cases and 40 controls enrolled, we observed a positive association between each of the early life exposures and development of EoE (antibiotics in infancy, OR = 4.64, 95% CI = 1.63-13.2; Cesarean delivery, OR = 3.08, 95% CI = 0.75-12.6; preterm delivery, OR = 2.92, 95% CI = 0.71-12.0; NICU admission, OR = 4.00, 95% CI = 1.01-15.9). Results were unchanged after adjusting for potential confounders, though only early antibiotic use had CIs that did not cross 1.0. Moderate to strong agreement was observed between 54 subject-mother pairs (antibiotics, K = 0.44, P = 0.02; Cesarean delivery, K = 1.0, P < 0.001; preterm delivery, K = 0.80, P < 0.001; NICU, K = 0.76, P < 0.001). In sum, antibiotics in infancy was significantly associated with increased risk of EoE diagnosed in adulthood, while positive trends were seen with other early life factors such as Cesarean delivery, preterm delivery, and NICU admission. This may indicate persistent effects of early life exposures and merits additional study into conserved pathogenic mechanisms.

Long-term Continued Proton Pump Inhibitor Use is Common in Patients Diagnosed with Eosinophilic Esophagitis Despite Failure of Histologic Response: Data from a two-centre study: Long-term PPI Use in Patients with EoE.

Background and Aims: Treatment paradigms for proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE) are evolving. We aimed to determine patterns of long-term PPI use after EoE diagnosis in PPI histologic non-responders. Methods: We conducted a retrospective review at University of Colorado (UCH) and University of North Carolina (UNC) of EoE patients who were histologic non-responders to PPIs. Data were extracted from electronic medical records related to demographics, PPI use, and reasons for continuing or stopping PPI. Results: Of 67 patients in the UCH cohort, PPIs were initially discontinued in 9 (13%). Of 58 remaining on PPI, 48% were not instructed to discontinue therapy and 26% continued for symptom improvement. Of 675 patients at UNC, PPI was stopped in 185 (27%). Of patients remaining on PPI, 15% were not told to discontinue therapy and 62% were continued for symptom improvement. At last contact, >50% of patients remained on PPI at both centres with most common reasons for continuation being symptom improvement and not telling patients to discontinue. In the UNC cohort, clinical features associated with remaining on PPI included children younger than 18 years (p=0.01), males (p<0.001), heartburn symptoms (p<0.001) and hiatal hernia (p=0.004). Patients with dysphagia were less likely to remain on PPIs (p<0.001). Conclusions: Long-term PPI use is common in EoE patients even without histologic response. Failure to instruct patients to discontinue therapy was a common reason for long-term use, thus PPI use should be revisited in all EoE patients to confirm clinical benefit.

Distal esophagus is the most commonly involved site for strictures in patients with eosinophilic esophagitis.

While strictures are common in eosinophilic esophagitis (EoE), there are few data on stricture distribution and characteristics. Our primary aim was to characterize strictures by location in the esophagus in EoE and associated clinical, endoscopic, and histologic features. This was a retrospective study from the UNC EoE Clinicopathologic Database of subjects with esophageal strictures or narrowing from 2002 to 2017. Strictures were categorized as distal esophagus/gastroesophageal junction, mid-esophagus, proximal esophagus, or diffusely narrowed. Stricture location was assessed and compared with clinical, endoscopic, and histologic features, and also with treatment response to diet or topical steroids. Efficacy of combination therapy with dilation and intralesional steroid injection was assessed in a sub-group of patients with strictures. Of 776 EoE cases, 219 (28%) had strictures, 45% of which were distal, 30% were proximal, 5% were mid-esophageal, and 20% had diffuse narrowing. Those with mid-esophageal strictures were younger (P = 0.02) and had shorter symptom duration (P < 0.01). Those with diffuse esophageal narrowing were more likely to be women (57%) and have abdominal pain (25%). There was no association between other clinical, endoscopic, and histologic findings and treatment response based on stricture location. Fourteen patients (8%) received intralesional triamcinolone injection and subsequently achieved a higher mean dilation diameter after injection (13.7 vs. 15.5 mm; P < 0.01). In conclusion, almost half of strictures in EoE patients were in the distal esophagus. Therefore, EoE should be a diagnostic consideration in patients with focal distal strictures and not presumed to be secondary to gastroesophageal reflux disease.

Compounded Oral Viscous Budesonide is Effective and Provides a Durable Response in Eosinophilic Esophagitis.

AIM: Because no approved medications exist for eosinophilic esophagitis (EoE), patients must use off-label drugs or create their own formulations. We assessed the efficacy of a standardized compounded budesonide suspension for treatment of EoE. MATERIALS AND METHODS: We conducted a retrospective cohort study of EoE patients at the University of North Carolina treated with compounded budesonide dispensed by a specialty compounding pharmacy. Outcomes (symptomatic global response [yes/no], endoscopic response [% with individual findings], and histologic response [absolute eosinophil count; % with <15 eos/hpf])were assessed after the initial and last treatment in our system. RESULTS: We identified 48 patients treated with compounded budesonide (mean age 33.6; 69% male; 96% white; 2.4 mg mean initial dose). After a mean length of follow-up of 17.0 months (range: 4.2 - 56.3), there was a significant decrease in symptoms of dysphagia (95% vs. 32%, p < 0.001), improvements in heartburn (37% vs. 11%, p=0.06) and global symptom response (81%). The median of the peak eosinophil counts decreased from 55 to 20 eos/hpf (p<0.001) with 42% achieving a response of <15 eos/hpf. Esophageal candidiasis was rare (6%). In the 18 patients with prior non-response to corticosteroids or dietary elimination, 83% had symptomatic and 38% had histologic response. CONCLUSION: Compounded budesonide suspension produced a durable symptomatic, endoscopic, and histologic response in a cohort followed for more than a year. Many patients previously refractory to prior therapy responded to compounded budesonide. This formulation can be used clinically until there are approved drugs with esophageal formulations for EoE.

Prolonged Time to Diagnosis of Eosinophilic Esophagitis Despite Increasing Knowledge of the Disease.

Eosinophilic esophagitis (EoE) is a chronic condition characterized by eosinophilic-predominant inflammation and esophageal dysfunction.1,2 EoE represents a rapidly increasing cause of morbidity and a growing health problem.

Progression from an Inflammatory to a Fibrostenotic Phenotype in Eosinophilic Esophagitis.

Previous studies have suggested that eosinophilic esophagitis (EoE) progresses from chronic inflammation to fibrostenosis. However, natural history data illustrating this progression in individual patients are lacking. Here, we present 6 patients who progressed from an inflammatory to a fibrostenotic phenotype of EoE in the absence of treatment. At the time of diagnosis, none of the patients had significant evidence of fibrostenosis, but they did have other inflammatory findings of EoE such as edema, linear furrows, or exudates. After being lost to follow-up and treatment for an average of 7.8 ± 2.0 years, strictures (n = 5; 83%) or a small-caliber esophagus (n = 4; 67%) were present in a majority of the patients, and the majority required esophageal dilation. These cases confirm that EoE can progress from an inflammation-only phenotype to a fibrostenotic phenotype in certain patients.

Increased Long-Term Mortality among Black CABG Patients Receiving Preoperative Inotropic Agents.

The aim of this study was to examine racial differences in long-term mortality after coronary artery bypass grafting (CABG), stratified by preoperative use of inotropic agents. Black and white patients who required preoperative inotropic support prior to undergoing CABG procedures between 1992 and 2011 were compared. Mortality probabilities were computed using the Kaplan-Meier product-limit method. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 15,765 patients underwent CABG, of whom 211 received preoperative inotropic agents within 48 hours of surgery. Long-term mortality differed by race (black versus white) among preoperative inotropic category (inotropes: adjusted HR = 1.6, 95% CI = 1.009-2.4; no inotropes: adjusted HR = 1.15, 95% CI = 1.08-1.2; P(interaction) < 0.0001). Our study identified an independent preoperative risk-factor for long-term mortality among blacks receiving CABG. This outcome provides information that may be useful for surgeons, primary care providers, and their patients.