Amindra S. Arora

Prevalence and Predictive Factors of Eosinophilic Esophagitis in Patients Presenting With Dysphagia: A Prospective Study

OBJECTIVES:Eosinophilic esophagitis (EE) is an increasingly recognized cause of dysphagia. We prospectively assessed the prevalence of EE using midesophageal biopsies in patients presenting with no endoscopically evident cause of dysphagia. We also aimed to determine the clinical and endoscopic factors predictive of EE in outpatients undergoing endoscopy for dysphagia.METHODS:Outpatients (18–60 yr of age) undergoing endoscopy for dysphagia at Mayo Clinic, Rochester between June 2005 and June 2006 were enrolled. Patients completed the validated Mayo Dysphagia Questionnaire (MDQ). Biopsies were obtained from the midesophagus if there was no endoscopically evident cause of dysphagia or there were endoscopic findings suggestive of EE. EE was defined as the presence of >20 eosinophils/high-power field. Logistic regression was performed to identify predictors of EE.RESULTS:Of 376 patients enrolled, 238 (63%) completed the MDQ and 222 (59%) had midesophageal biopsies; 33 (15%, 95% CI 6%–12%) had EE by biopsy. Ten of 102 (9.8%) patients who appeared endoscopically normal had EE by biopsy, while 8 of 21 (38%) patients with endoscopic changes suggestive of EE had EE on biopsy. Predictors of EE were younger age, endoscopic features suggestive of EE, absence of use of proton pump inhibitors, and a history of any food impaction for greater than 5 min.CONCLUSIONS:Midesophageal biopsies from normal-appearing mucosa should be obtained in all patients with unexplained solid food dysphagia; this may diagnose EE in about one in 10 cases.

Swallowed Fluticasone Improves Histologic but Not Symptomatic Response of Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE). METHODS We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 μg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response. RESULTS A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05). CONCLUSIONS Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE.

Eosinophilic esophagitis: asthma of the esophagus?

Eosinophilic esophagitis (EE) is rapidly emerging as a distinct disease entity in both pediatric and adult gastroenterology. The typical clinical presentation includes solid food dysphagia in young men who have an atopic predisposition. Food impaction necessitating endoscopic intervention is common. EE should be suspected, in particular, in patients with unexplained dysphagia or those with no response to antacid or anti-acid secretory therapy. Careful endoscopic and radiographic examinations reveal furrows, corrugations, rings, whitish plaques, fragile crêpe paper-like appearance, and a small-caliber esophagus. Mucosal erosion in the distal esophagus, characteristic to reflux esophagitis, is absent in EE. Marked eosinophil infiltration in the esophageal epithelia (>20 eosinophils per high-power field) is the diagnostic hallmark. Food antigens and aeroallergens may play a role in the pathogenesis of EE. The mechanisms may be dependent or independent of immunoglobulin E. Elimination diets, systemic and topical corticosteroids, leukotriene receptor antagonists, and, most recently, an anti-interleukin-5 monoclonal antibody have been used to treat EE. EE likely represents another example of eosinophil-associated inflammation of epithelia at the interface between external and internal milieu, similar to bronchial asthma and atopic dermatitis. This review summarizes recent progress in the diagnosis and management of EE and discusses future research directions.

Erratum: 3-Yr Follow-Up of Topical Corticosteroid Treatment for Eosinophilic Esophagitis in Adults

BACKGROUND:Eosinophilic esophagitis (EE) is a clinicopathologic syndrome comprising isolated eosinophilic inflammation of the esophagus, with symptoms of dysphagia, and possibly, reflux. It was initially described in children, and in recent years, there is a heightened awareness in adults. The etiology is not completely understood. The treatments include dietary manipulation, topical corticosteroids, systemic corticosteroids, Montelukast, and endoscopic dilation. In adults, there are no randomized trials demonstrating the efficacy of any particular treatment, and no prospective studies describing the natural history of the disease following treatment.METHODS:We performed an interval follow-up of patients treated with a swallowed corticosteroid inhaler. We contacted 51 adult patients who were diagnosed with EE and treated with a swallowed corticosteroid inhaler between September 1, 1999, and May 31, 2003. All patients had received 6 wk of treatment with fluticasone 220 mEq/puff, four puffs swallowed twice daily for 6 wk.RESULTS:Thirty-two patients replied (63%) with a mean follow-up duration of 3.3 yr. Ninety-one percent of patients reported recurrent symptoms; a mean of 8.8 months after treatment was completed. Sixty-nine percent of patients repeated treatment with the steroid inhaler at least once.CONCLUSIONS:It appears that EE is a chronic remitting disorder that requires more than one topical steroid treatment course.

Metastatic Malignant Melanoma of the Gastrointestinal Tract

Malignant melanoma is one of the most common malignancies to metastasize to the gastrointestinal (GI) tract. Metastases to the GI tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and melena. We report 2 cases of malignant melanoma metastatic to the GI tract, followed by a review of the literature. The first case is a 72-year-old man who underwent resection of superficial spreading melanoma on his back 13 years previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a gastric fundus noted during endoscopy was taken and revealed metastatic malignant melanoma, which was resected 1 month later. Three weeks later, the patient was found to have an ulcerated jejunal metastatic melanoma mass, which was also resected. The second case is a 63-year-old man with an ocular melanoma involving the chorold of the left eye that had been diagnosed 4 years previously, which had been excised several times, who presented with anorexia, dizziness, and fatigue. He was found to have cerebellar and stomach metastases. He underwent adjuvant radiation therapy, chemotherapy, and surgical resection of the gastric melanoma metastasis. In patients with a history of melanoma, a high index of suspicion for metastasis must be maintained if they present with seemingly unrelated symptoms. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains. Management may include surgical resection, chemotherapy, immunotherapy, observation, or enrollment in clinical trials. Prognosis is poor, with a median survival of 4 to 6 months.

Infliximab-Associated Reversible Cholestatic Liver Disease

Infliximab, a novel therapy for Crohn disease, has been shown to be both safe and effective. We describe a 44-year-old woman with Crohn disease who developed jaundice after an infusion of infliximab. Multiple investigations were undertaken, cholestatic liver disease was diagnosed, and her condition improved with supportive therapy. Although likely a rare adverse event, cholestatic liver injury should be considered in patients presenting with jaundice who have received infliximab therapy.

Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis.

OBJECTIVES:Eosinophilic esophagitis (EoE) is characterized by infiltration of eosinophils into esophageal epithelium. Blood levels of an eosinophil granule protein, eosinophil-derived neurotoxin (EDN), have been proposed as a biomarker for EoE. However, information regarding localization of EDN in the diseased tissues has not been available. The goal of this study was to evaluate the magnitude and distribution of EDN deposition in tissue specimens from the esophagus of EoE patients.METHODS:We studied specimens from 10 adult EoE patients and eight histologically normal controls (three under age 17). Sections from mid-esophageal biopsy specimens were stained for EDN by immunofluorescence, using a polyclonal rabbit antibody to EDN. Cellular staining (i.e., infiltration of intact eosinophils) and extracellular staining (i.e., deposition of released EDN) were scored in a blinded manner on an established 7-point scale.RESULTS:Esophageal biopsy specimens from histologically normal controls showed no or few intact eosinophils and no or minimal extracellular EDN deposition. In contrast, EDN staining was clearly observed in specimens from all EoE patients. In some EoE patients, marked extracellular EDN deposition was observed despite relatively small numbers of intact eosinophils. Overall, there was no correlation between the eosinophil infiltration and the extracellular EDN staining scores.CONCLUSIONS:Marked tissue deposition of extracellular EDN is present in the esophagus of EoE patients. Tissue eosinophil counts may underestimate how extensively eosinophils are involved, particularly in individuals with marked eosinophil degranulation. Evaluation of EDN staining in esophageal biopsy specimens may be useful to diagnose and manage patients with EoE.

Occurrence of and risk factors for complications after endoscopic dilation in eosinophilic esophagitis

BACKGROUND Several small series have suggested an increased risk of complications associated with esophageal dilation in patients with eosinophilic esophagitis (EoE). OBJECTIVE To quantitate the risk and identify risk factors for esophageal complications in dilation in EoE patients. DESIGN Retrospective, uncontrolled, single-center study. SETTING Tertiary referral hospital. PATIENTS A total of 161 EoE patients (mean ± standard deviation age 44.3 ± 15.3 years, 112 men, 49 women, 150 white patients, 10 unknown, 1 Asian). INTERVENTIONS Through-the-scope balloon or Savary dilation of EoE. MAIN OUTCOME MEASUREMENTS The rate of complications defined as deep mucosal tear, major bleeding, or perforation, and determination of risk factors for complications. RESULTS A total of 293 dilations were performed in 161 patients. Complications reported were deep mucosal tear in 9.2% (n = 27), major bleeding in 0.3% (n = 1), and immediate perforation in 1.0% (n = 3). All patients with perforations were successfully treated medically without surgery (mean ± standard deviation hospital stay 5.3 ± 3.2 days). Factors associated with an increased risk of complications were luminal narrowing in the upper (odds ratio [OR], 5.62; 95% CI, 2.07-15.26; P < .001) and middle third of the esophagus (OR, 4.93; 95% CI, 1.64-14.83; P < .005) compared with lower third, luminal stricture unable to be traversed with a standard upper endoscope (OR, 2.48; 95% CI, 1.06-5.83; P = .037), and use of Savary dilator (OR, 2.63; 95% CI, 1.18-5.83; P = .018). LIMITATIONS Retrospective design, uncontrolled study. CONCLUSIONS Deep mucosal tears are common after dilation (9%), but the risk of immediate transluminal perforation with EoE is approximately 1%. The risk of severe complications is increased in patients with more proximal stricture and strictures that initially prevent endoscope passage.

Allergen-Specific In Vitro Cytokine Production in Adult Patients with Eosinophilic Esophagitis

Although the pathogenesis of eosinophilic esophagitis (EE) likely involves hypersensitivity reactions against exogenous allergens, allergen-specific cellular immune responses have not been studied. We investigated allergen-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in adult patients with EE (n=15) and healthy controls (HC; n=9). PBMCs were incubated with nine common food and environmental allergens or a nonspecific mitogen, and the levels of interleukin (IL)-5, IL-10, IL-13, and interferon-γ in the cell-free supernatants were determined. Spontaneous and mitogen-stimulated cytokine production did not differ between EE and HC. House dust mite, ragweed, Aspergillus, milk, and soy induced significantly higher IL-5 production in EE (P < 0.05). House dust mite also augmented IL-13 production in EE (P < 0.05). Furthermore, PBMCs from three EE patients without allergen-specific IgE vigorously produced IL-5 and IL-13 on allergen stimulation. Thus, immune responses in EE are characterized by enhanced production of Th2-like cytokines against both food and environmental allergens.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.