Concomitant Eosinophilic Esophagitis Research Articles

Eosinophilic Gastritis and Enteritis Are Increased in Families With Eosinophilic Esophagitis.

There are limited data on the familial risk of distal eosinophilic gastrointestinal diseases (EGIDs) in patients with eosinophilic esophagitis (EoE). We analyzed the risk of eosinophilic gastritis/gastroenteritis (EG/EGE) and eosinophilic colitis (EC) as forms of distal EGIDs using International Disease Classification-9/10 codes in subjects with EoE and their relatives. The Utah Population Database is a resource that links genealogy information and medical records in Utah. We identified EGIDs in probands and their first-degree (FDRs), second-degree (SDRs), and third-degree (TDRs) relatives in the Utah Population Database. Relative risk and 95% confidence intervals were estimated. All individuals with inflammatory bowel disorder were eliminated to avoid misdiagnosis with EGIDs. We included 8,455 subjects with EoE, 396 with EG/EGE, and 172 with EC. Probands with EoE were at increased risk of EG/EGE and EC. Risks of EG/EGE were increased among FDRs and SDRs of probands with EoE , even without concomitant EoE in the relatives. Increased risk of EG/EGE in FDRs and SDRs was also present for EoE probands without EG/EGE or EC. We observed no isolated familial aggregation of EG/EGE after excluding cases with comorbid EoE. EC probands without EoE were at increased risk of EG/EGE, but no evidence of familial risk of EC was observed. The relative risk of EG/EGE is significant among relatives of patients with EoE, suggesting that shared genetic factors exist among these EGIDs. EG/EGE and EC showed limited familial clustering, although sample sizes were small.

Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use

BackgroundDupilumab has been approved to treat atopic dermatitis, asthma, and nasal polyps and is in active clinical trials for the treatment of eosinophilic esophagitis (EoE). Given its shared immunopathology, we hypothesized that EoE symptoms and inflammation would improve when dupilumab therapy was used for other allergic indications. ObjectiveTo measure the clinical and histologic response in EoE to dupilumab when treating other atopic diseases. MethodsWe completed a retrospective chart review of all patients at Children's Hospital of Philadelphia and Rady Children Hospital who were prescribed dupilumab for atopic dermatitis, asthma, or nasal polyps and had a concomitant clinical diagnosis of EoE. Demographic information along with histology, symptom scores, medications, and diet information were collected. Response to dupilumab was evaluated. ResultsA total of 45 patients were identified. Of which, 11 patients were prescribed dupilumab for asthma, 27 for atopic dermatitis, 3 for nasal polyps, and 4 for compassionate use for EoE. There was no follow-up data for 8 patients. Follow-up histology was available for 26 patients: 22 of 26 had less than 6 eosinophils per high power field after the initiation of dupilumab with significant improvement (pre: 52.9 + 35.1 to post: 4.5 + 10.9 eosinophils/high power field, P < .005). A total of 28 patients had improvement of symptoms, with 24 patients reporting complete resolution of symptoms after dupilumab initiation. Reductions in EoE treatment medications (swallowed steroids, proton pump inhibitors) or expansion of diet occurred in 29 patients treated with dupilumab. ConclusionDupilumab therapy initiated for atopic disease effectively induces symptomatic and histologic remission of esophageal disease and reduces the need for EoE-directed therapy in patients with concomitant EoE.

Phenotype and Natural History of Inflammatory Bowel Disease in Patients With Concomitant Eosinophilic Esophagitis.

The co-occurrence of autoimmune diseases is well recognized. Though studies have suggested that eosinophilic esophagitis (EoE) is more common in patients with inflammatory bowel diseases (IBD), whether co-occurrence of EoE modifies natural history of IBD is unknown. This was a retrospective case-control study at a referral center. Cases consisted of patients with IBD and EoE, with both diseases diagnosed using established criteria. Controls comprised patients with IBD without concomitant EoE. Two controls were selected per case and were matched for duration of IBD. Relevant covariates regarding disease presentation and natural history were extracted from the medical record and compared between the 2 groups. A total of 95 IBD-EoE cases and 190 IBD controls were included in our study. The IBD-EoE group was diagnosed with IBD at a younger age than those with IBD alone (22.3 years vs 29.0 years; P < 0.001) and were more likely to be male (80.0% vs 45.8%; P < 0.001). There were no differences in medical or surgical therapy for IBD between the 2 groups. Among those with IBD-EoE, patients for whom IBD was diagnosed first presented more commonly with dysphagia (50.8% vs 26.9%; P = 0.04) and endoscopically had evidence of esophageal rings (50.0% vs 23.1%; P = 0.02) when compared with those where EoE was diagnosed first. Patients with concurrent IBD-EoE are diagnosed at a younger age and more likely to be males but have similar natural history as those without EoE. There were differences in EoE phenotype based on whether the EoE or IBD was diagnosed first.

Is There a Role for pH Impedance Monitoring in Identifying Eosinophilic Esophagitis in Children with Esophageal Atresia?

To evaluate clinical, endoscopic, and pH-impedance measures in a cohort of children with esophageal atresia and concomitant eosinophilic esophagitis (EoE) and compared it with disease-matched controls, to identify predictive factors for the development of EoE and esophageal stricture. We reviewed 63 patients with esophageal atresia assessed for refractory upper gastrointestinal symptoms between January 2015 and September 2017 at 2 tertiary referral centers. All patients underwent upper gastrointestinal endoscopy and pH-impedance monitoring. Based on esophageal histology, patients were classified as (1) esophageal atresia without evidence of esophagitis; (2) esophageal atresia with evidence of esophagitis (including esophageal eosinophilia not meeting the criteria for EoE); (3) esophageal atresia with concomitant EoE. Age and sex matched patients with gastroesophageal reflux disease were used as disease controls. The presence of atopy and peripheral eosinophilia at baseline were significantly associated with EoE (P<.05). Although there was a tendency toward an increased number of strictures in patients with esophageal atresia-EoE, this did not reach statistical significance (P=.06). Higher esophageal acid exposure time and lower baseline impedance values were significantly associated with eosinophilic infiltration (P<.05 and P<.01, respectively). Using logistic regression analysis, the presence of mucosal eosinophilia was the most predictive factor for stricture formation (P<.05). A history of atopy and the presence of peripheral eosinophilia in patients with esophageal atresia are predictive factors for the development of EoE, which in turn is a predictive factor for stricture occurrence. Higher esophageal acid exposure time and lower baseline impedance are associated with esophageal eosinophilic infiltration, suggesting their value in selecting which patients with esophageal atresia should undergo endoscopic examination.

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Issue Highlights

A Statistically Significant Association Between Esophageal Granular Cell Tumors and Eosinophilic Esophagitis: A 16-year Analysis at Two Large Hospitals of 167,434 EGDs.

Esophageal granular cell tumor (eGCT) is a rare, usually benign, neoplasm of neuroectodermic origin. Eosinophilic esophagitis (EoE) is a relatively uncommon, immune-mediated, chronic disease. Both diseases commonly present with dysphagia. One case has been reported of simultaneous occurrence of both diseases. To determine the association between diseases. The present study was an IRB-approved, retrospective review of esophagogastroduodenoscopies (EGDs) with esophageal biopsies from two large hospitals, 1999-2014. Among 29,235 EGDs with esophageal biopsies for 16years (167,434 total EGDs), 16 patients had pathologically diagnosed eGCT, and 1225 patients had pathologically diagnosed EoE. Five (31%) of 16 patients with eGCT had concomitant EoE (p=0.001, OR 10.43, 95% ORCI 3.16-32.44, Fisher's exact test). Patients with simultaneous eGCT and EoE were young (mean age=33.6±12.9years). Three were female. Dysphagia was presenting symptom in 4 (80%) of patients. Three had asthma. All five patients had >20 eosinophils/hpf in esophageal biopsy specimens. Three patients had endoscopic esophageal abnormalities suggesting EoE. Four patients were treated with a PPI (before and after diagnosis of EoE), and 2 patients underwent six-food-elimination diet with partial symptomatic improvement. The eGCTs averaged 13.4±4.2mm in maximal diameter and were located in upper-2, middle-2, and lower esophagus-2 (1 patient had 2 eGCTs). eGCTs were endoscopically resected-3 patients, and monitored-2 patients. Surveillance endoscopies revealed no recurrence or growth of eGCTs after resection (mean follow-up=4.6years). This novel report of 5 patients with simultaneous EoE and eGCT adds to one, previously published case and suggests these two diseases are associated, and have a common pathophysiologic link, despite apparently different pathogenesis. Large, prospective, endoscopic and pathologic studies are warranted to further investigate this association.

Attenuation of Endoscopic Inflammatory and Stenotic Features in Patients with Co-existing Eosinophilic Esophagitis and Inflammatory Bowel Disease

Introduction: Eosinophilic esophagitis (EoE) has become an increasingly well-described disease entity characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation of esophageal mucosa. EoE has been associated with atopic and autoimmune diseases. This study compares clinical and endoscopically identified esophageal manifestations of patients with EoE and inflammatory bowel disease (IBD) concomitantly to patients with EoE alone. Methods: Data from 22 patients with concomitant EoE and IBD (64% with Crohn's disease) and 50 control patients with EoE alone between 1993 and 2014 was retrospectively evaluated. Clinical charts of patients between ages 18-80 years old were identified using ICD-9 codes (EoE: 530.13; CD: 555.9, 555.1, 555.2, 555.0; UC: ICD-9 556.9, 557.0, 556.5, 556.3, 556.6) by our Enterprise Data Warehouse (EDW). EoE controls were tested to not be statistifically significantly different from patients with concomitant EoE and IBD in gender, race, or age. Demographic and disease-specific characteristics, endoscopic findings using a validated instrument (EoE Endoscopic Reference Score), histopathology, and treatment in patients with concomitant IBD and EoE were examined. Bivariate analysis with the chi-square test was used to look for statistical significance between the two groups.Table 1: Demographics and Disease-specific Characteristics of Concomitant EoE and IBD Compared to EoE AloneResults: Patients with concomitant EoE and IBD compared to EoE alone were found to have significantly less strictures (9% vs 58%, p=0.0001), furrows (64% vs 92%, p-0.003) and exudates (18% vs 56%, p=0.003) on endoscopy (Table and Figure 1). Of the 22 patients with concomitant EoE and IBD, 11 patients (50%) were treated with immunomodulators including anti-TNF agents, 6-MP, azathioprine and methotrexate for IBD, and 0/11 of these patients had strictures. Patients with EoE and IBD compared to EoE alone were also found to present less frequently with dysphagia as an initial symptom (68% vs 88%, p=0.04).Figure 1Conclusion: Patients with concomitant EoE and IBD demonstrated significantly lower prevalence of endoscopically identified inflammatory (furrows, exudate) and remodeling (stricture) features compared to EoE patients alone. The decreased activity of EoE in patients with concomitant EoE and IBD may be related to immunomodulator therapy used to treat IBD or earlier diagnosis of EoE owing to healthcare utilization amongst IBD patients.

Swiss Cheese Esophagus: A Case of Esophageal Intramural Pseudodiverticulosis

Diverticula can be seen throughout the gastrointestinal tract including the Esophagus. Esophageal Intramural Pseudodiverticulosis (EIPD) is a rare condition characterized by the presence of multiple pinhead-sized outpouchings of the esophageal wall, giving the esophagus the appearance of Swiss cheese on endoscopy. We present a case of EIPD in a patient with eosinophilic esophagitis (EoE). To our knowledge, this is the first case describing EIP with concomitant EoE. A 72 year old Caucasian male presents to a gastroenterology clinic for evaluation of dysphagia. He underwent endoscopy as part of his evaluation, which revealed multiple esophageal diverticula as well as distal esophageal strictures. The patient underwent successful esophageal stricture dilation and was advised to follow up for a repeat endoscopy. He followed with another gastroenterologist for the next 3 years where he was diagnosed with Eosinophilic Esophagitis (EoE). He was treated with oral budesonide slurry but continued to have recurrent dysphagia. He presented with a complaint of “macaroni stuck” in his throat. The food bolus passed spontaneously and on endoscopy he had multiple esophageal rings as well as pseudodiverticulosis. The patient underwent Savary dilation, followed by multiple repeat stricture dilatation sessions in the following months. He subsequently had complete resolution of his dysphagia, while on budesonide, and had a satisfactory endoscopic appearance on the most recent endoscopy, except for the pseudodiverticulosis. EIPD was first described in 1960 by the British Institute of Radiology. To date a little over 200 cases of EIP have been described in the literature. Unlike colonic diverticula, the exact mechanism by which EIPD forms is unclear. It seems, however, to be affected by chronic inflammation whereby the structural integrity of the esophageal lining, especially at the excretory ducts of the submucosal glands, is compromised leading to the formation of diverticula. This rare entity represents a unique challenge, especially in the presence of other concomitant conditions. In our patient, both EoE and EIPD can lead to dysphagia and stricture formation. This raises an interesting question: Are the strictures a result of EIPD or EoE or both? Also, if EIPD is associated with chronic inflammatory states then why is it not more commonly seen with conditions such as reflux esophagitis?Figure 1

Eosinophilic Laryngitis in Children with Aerodigestive Dysfunction.

To describe the presence of laryngeal eosinophils and associated symptomatology in patients with aerodigestive dysfunction. Case series with chart review. Single tertiary pediatric referral center. Eighty-one consecutive pediatric patients referred to a multidisciplinary aerodigestive clinic with upper airway concerns. Microlaryngoscopy and posterior arytenoid biopsy, flexible bronchoscopy, esophagogastroduodenoscopy and esophageal biopsy, and impedance probe testing were performed as indicated by clinical symptoms. Positive versus negative posterior arytenoid biopsy for eosinophils and the presence or absence of concomitant histopathological laryngitis and/or esophagitis were measured. Nine of 81 (11%) patients had positive laryngeal biopsy for eosinophils (range, 1-29 eosinophils/high-powered field [HPF]). Three of these 9 patients also had concurrent biopsy-proven eosinophilic esophagitis, while 8 of 81 total patients had biopsy-proven eosinophilic esophagitis. The frequency of biopsy-proven eosinophilic esophagitis was higher in patients with posterior arytenoid eosinophils versus patients without laryngeal eosinophils (33% versus 6.9%, P = .0408). Eosinophilic inflammation in the larynx has not been described in children with complex aerodigestive complaints. Posterior arytenoid eosinophils may serve as a marker of chronic laryngeal inflammation in children with aerodigestive dysfunction, although their exact role in this inflammation remains unclear. In our population, >15 eosinophils/HPF within posterior arytenoid biopsies was associated with concomitant eosinophilic esophagitis.

Increased Risk of Esophageal Eosinophilia and Eosinophilic Esophagitis in Patients With Active Celiac Disease on Biopsy

The possible association between eosinophilic esophagitis (EoE) and celiac disease is controversial because prior results have been contradictory. We aimed to determine the relationship between EoE and celiac disease among patients with concomitant esophageal and duodenal biopsies. We conducted a cross-sectional study in a U.S. national pathology database by using data from January 2009 through June 2012. Our primary case definition was defined by the presence of esophageal eosinophilia with ≥15 eosinophils per high-power field. The crude and adjusted (for age and sex) odds of esophageal eosinophilia for patients with active celiac disease were compared with those without celiac disease. Sensitivity analyses were performed by using more stringent case definitions and by estimating the associations between celiac disease and reflux esophagitis and celiac disease and Barrett's esophagus. Of 292,621 patients in the source population, 88,517 with both esophageal and duodenal biopsies were studied. Four thousand one hundred one (4.6%) met criteria for EoE, and 1203 (1.4%) met criteria for celiac disease. Odds of EoE were 26% higher in patients with celiac disease than in patients without celiac disease (adjusted odds ratio [aOR], 1.26; 95% confidence interval [CI], 0.98-1.60). The magnitude of association varied according to EoE case definition, but all definitions showed a weak positive association between the 2 conditions. There was no association between celiac disease and reflux esophagitis (aOR, 0.95; 95% CI, 0.85-1.07) or Barrett's esophagus (aOR, 0.89; 95% CI, 0.69-1.14) and celiac disease. There is a weak increase in EoE in patients with celiac disease. This association strengthened with increasingly stringent definitions of EoE and was not observed for other esophageal conditions. In patients with celiac disease, concomitant EoE should be considered in the correct clinical setting.

A Case of Eosinophilic Esophagitis With Achalasia Requiring Myotomy

Introduction: Eosinophilic esophagitis (EoE) is a clinicopathological disorder defined by esophageal dysfunction and eosinophilic infiltration of the esophagus with more than 15 eosinophils per high power field (hpf) on microscopy after ruling out other causes of eosinophilia. Dysphagia is the most common symptom first described in a 1978 case report. Esophageal dysmotility on esophageal manometry has been described in EoE patients. Only one case report documented successful management of EoE with concomitant achalasia via Heller’s myotomy. Our patient demonstrates EoE in the presence achalasia with persistent symptoms despite medical management requiring Heller myotomy for symptomatic improvement. A 48-year-old female presented to clinic with difficult, painful swallowing and food regurgitation. She was diagnosed with EoE one year prior and treated with PPI followed by swallowed fluticasone, but did not achieve reduction in eosinophil count until she started a six food elimination diet. Despite histologic improvement, her symptoms persisted. She underwent upper endoscopy at our institution revealing a narrow-caliber esophagus that was subsequently dilated. Mucosal features were consistent with EoE. Biopsies showed up to 18 intraepithelial eosinophils per hpf from the proximal esophagus. She subsequently underwent high resolution esophageal manometry (EM) revealing achalasia. The esophagus exhibited failed peristalsis without relaxation of the lower esophageal sphincter (LES). The patient underwent laparoscopic Heller myotomy with Nissen fundoplication providing nearly complete resolution of symptoms. There are few reports of achalasia in the setting of EoE since the 1978 case. One case series reported most patients with EoE have abnormalities on EM. Only one patient had achalasia, which resolved with inhaled fluticasone. Another case series identified that 4 of 512 cases of achalasia had concomitant EoE. Two patients were treated for achalasia with Heller myotomy, but symptoms recurred. A recent study evaluating EoE with high resolution EM shows that esophageal body motility abnormalities, namely weak or failed peristalsis, are most common. It is unclear if our patient has type 1 or type 2 achalasia as stratified by the Chicago Classification since panesophageal pressurization may be seen in EoE alone. EoE with achalasia may be resistant to medical management and require myotomy for symptom improvement. EoE patients may benefit from early EM studies to identity concurrent esophageal motility abnormalities.

Review of Treatment Outcomes in Pediatric Patients with Concomitant Eosinophilic Esophagitis and Celiac Disease

Review of Treatment Outcomes in Pediatric Patients with Concomitant Eosinophilic Esophagitis and Celiac Disease

Association of achalasia and eosinophilic esophagitis

Various esophageal motor disorders including achalasia have been sporadically reported in patients with eosinophilic esophagitis (EoE). The aim of this study was to determine the association between achalasia and EoE and to review the treatment outcomes in patients having both conditions. A retrospective search was conducted to identify the cases of achalasia having EoE over the last 10years at a tertiary care hospital in the United States. Subsequently, a review of the literature was performed to search for cases of achalasia that have concurrent EoE. The retrospective study showed that 4 out of 512 patients of achalasia (<1%) had concomitant EoE. The eosinophil counts were high (80-100/hpf) but the classic endoscopic features of EoE were present in only one patient. Long term outcome following treatment including botox, myotomy and corticosteroids was generally poor. Sixteen patients have been reported in the literature out of which five patients were reported in detail. Patients had good short term response to various therapies. The long term outcomes have not been reported. These studies suggest that a concurrence of these two conditions, although rare, may occur and may not be recognized by usual endoscopic features of EoE. Long term treatment outcomes, distinct from short term in the literature, may be poor.