Emily Kern

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15. CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

The adult eosinophilic oesophagitis quality of life questionnaire: a new measure of health-related quality of life

Aliment Pharmacol Ther 2011; 34: 790–798

Qualitative assessment of patient-reported outcomes in adults with eosinophilic esophagitis

Goals This study aims to qualitatively describe experiences of adult patients diagnosed with eosinophilic esophagitis (EoE). Specifically, we aim to identify disease-specific concerns related to patient-reported outcomes in this population to inform clinical care and assessment. Background EoE is a chronic inflammatory disease of the esophagus and is increasingly recognized as a cause of dysphagia in adults. On the basis of its symptoms, limited and restrictive treatment options and potential for social and psychological impact, it is logical to expect that the health related quality of life of EoE patients would be an important outcome marker for assessment. Study Twenty-four EoE patients participated in semistructured interviews about their illness experiences. Participants also provided demographic and clinical data, and completed the Medical Outcome Study Short Form 12 to assess mental and physical function. Results Six themes emerged from qualitative analyses which centered around 3 main points: concerns about the illness itself, concerns about swallowing difficulty, and concerns about the impact of EoE on social interactions. Patients were generally open to disclosing their illness status and reported relief at receipt of the EoE diagnosis. EoE patients did not differ from healthy norms for physical well-being, and were similar to comparable illness groups for mental functioning. Conclusions Our study demonstrated that EoE has substantial impact on several psychosocial domains that are not adequately addressed by focused assessment of physical complaints of dysphagia. The results support the importance of development of disease-specific instruments pertaining to quality of life in EoE patients.

Prospective assessment of the diagnostic utility of esophageal brushings in adults with eosinophilic esophagitis

Patients with eosinophilic esophagitis (EoE) undergo multiple endoscopies with biopsy for both diagnosis and assessment of treatment response, which is inconvenient and costly. Brush cytology has been examined in Barretts esophagus to reduce the need for repeated endoscopic biopsies. The aim of this pilot study was to evaluate the ability of brush cytology to detect mucosal eosinophilia in patients with EoE. This prospective study included adults with untreated and treated esophageal eosinophilia undergoing endoscopy at a tertiary care center. Patients received paired brushings and biopsies at the proximal and distal esophagus. A blinded pathologist quantified the number of eosinophils and epithelial cells per high-power field (hpf) on the cytology slides. The ratio of eosinophils/epithelial cells was used to normalize the cytology specimens for density of cells collected. The main outcome measures were sensitivity and specificity of brush cytology, and correlation between cytology and histology. Twenty-eight patients enrolled. The average age of the cohort was 37.7 ± 10.4 years; 75% of subjects were male. The sensitivity of cytology was 67-69% at the proximal esophagus and 70-72% at the distal esophagus. The specificity was 61-67% proximally and 70-75% distally. Histology was not significantly correlated with the max ratio of eosinophils/epithelial cells per hpf or the absolute number of eosinophils on cytology slides. Cytology using esophageal brushing has limited sensitivity and specificity for the detection of esophageal mucosal eosinophilia. The presence of exudates on endoscopy increased the detection of eosinophilia, which could make cytology useful in pediatric EoE, which often has a more exudative presentation. Diagnostic yield may improve with alternative acquisition techniques or the incorporation of eosinophil degranulation proteins.

Emerging drugs for eosinophilic esophagitis

Introduction: Eosinophilic esophagitis (EoE) has emerged over the past two decades as an important esophageal disorder with significant associated morbidity. The prevalence of EoE now approximates that of commonly recognized gastrointestinal diseases including inflammatory bowel disease. In adults, EoE is now a leading cause of dysphagia and food impaction. Medications, food elimination diets and esophageal dilation are currently utilized for the treatment of EoE. While these approaches are often effective, no pharmaceutical agents have yet been approved by the Food and Drug Administration (FDA). The current medical therapies for EoE primarily consist of topical corticosteroids that have been adopted from formulations designed for pulmonary delivery in patients with asthma and have not been optimized for esophageal delivery. Areas covered: This article focuses on therapeutics being developed for EoE. Several trials have evaluated improved steroid vehicles designed for topical delivery to the esophagus. Novel biologic compounds, including anti-interleukin-5 and anti-interleukin-13, are being evaluated as targeted treatment options in EoE patients. Inhibitors of mast cell-derived prostaglandin D2 (PGD2) are also being studied, based on the concept that mast cells play an important role in EoE pathogenesis. Additional therapies, including immunomodulators, leukotriene antagonists, allergy immunotherapy and angiotensin II receptor blockers, are also examined in this article. Expert opinion: No FDA-approved prescription medications are currently available for EoE patients. Although a number of novel agents are being developed and tested, Phase III clinical trials are scarce. Since EoE is a newly described disease, physicians have an incomplete understanding of the diseases pathogenesis, natural history and disease manifestations. This has led to significant difficulties in determining the most appropriate endpoints of therapy. Clinical trials are hampered by the lack of an accepted, standardized disease activity measure or biomarker by which therapeutic efficacy is assessed. Effective and approved pharmaceutical therapies are eagerly awaited by both physicians and patients for this increasingly recognized and clinically important disease.

Liraglutide-Induced Autoimmune Hepatitis

IMPORTANCE Use of incretin-based hypoglycemic agents is increasing, but safety data remain limited. We treated a woman with marker-negative autoimmune hepatitis associated with the glucagon-like peptide 1 agonist liraglutide. OBSERVATIONS A young woman with type 2 diabetes mellitus and vitiligo presented with a 10-day history of acute hepatitis. Other than starting liraglutide therapy 4 months prior, she reported no changes in medication therapy and no use of supplements. At admission, aspartate aminotransferase level was 991 U/L; alanine aminotransferase level, 1123 U/L; total bilirubin level, 9.5 mg/dL; and international normalized ratio, 1.3. Results of a liver biopsy demonstrated interface hepatitis with prominent eosinophils and rare plasma cells. The patients liraglutide therapy was withheld at discharge but her symptoms worsened. A second biopsy specimen revealed massive hepatic necrosis. She started oral prednisone therapy for presumed liraglutide-induced marker-negative autoimmune hepatitis. CONCLUSIONS AND RELEVANCE This case represents, to our knowledge, the first report of liraglutide-induced autoimmune hepatitis. Hepatotoxicity may be an incretin analogue class effect with a long latency period. This case raises prescriber awareness about the potential adverse effects of glucagon-like peptide 1 agonists. Postmarketing studies are needed to define the hepatotoxic potential of these agents.

S1081 Patient Reported Outcomes in Adults With Eosinophilic Esophagitis

Background: Gastrointestinal illnesses are often associated with decreased health related quality of life (HRQOL). Eosinophilic Esophagitis (EoE) has emerged as an important cause of dysphagia and food impaction. The patients perspective on the disease has received little attention. The aim of this prospective study was to characterize HRQOL as it relates to patient reported outcomes in EoE. Methods: 23 adult patients (pts) with a diagnosis of EoE participated. Demographics, a dysphagia symptom score, SF-12v2 PCS and MCS, and an audio-recorded, 22-item structured interview were collected. Interview data were reviewed to identify common domains relating to HRQOL. Results: Mean (±SD) age was 39±2.5 years and 70% of subjects were male. Mean time since diagnosis was 1.5±0.4 years with symptomonset 11.5±2.5 years prior to diagnosis. 78%of patients rated dysphagia asmoderate or severe. Dysphagia frequency was 4±1.2 (weekly episodes). EoE pts had significantly higher PCS scores than norms for allergies, stomach disease, and diabetes (p<0.01). No differences were found when compared to healthy norms. EoE pts did not differ from illness groups for MCS, though were lower than healthy norms (p=.007). Interview data yielded domains related to HRQOL in EoE. 1) Fear/Anxiety/Frustration. Patients felt frustrated with the failure of past medical professionals to recognize their disease, and 74% felt relieved when diagnosed with EoE. During episodes of dysphagia, 57% expressed feelings of fear or panic, and 30% feared future episodes or episodes that would require ER visits. 2) Impact on Functioning. EoE caused public embarrassment or distress in 65% of patients, and resulted in modified eating habits in 87% of patients. 3) Feelings about the Disease. 26% of patients had concerns regarding the long-term consequences of the disease and the lack of research about the disease. Furthermore, 52% expressed fear that the disease would progress, and 48% were wary of medication side effects.Conclusions:Compared with other chronic illnesses, EoE pts reported significantly better physical health and similar mental health function. Exploratory interviews with adult EoE patients revealed that the disease impacts a number of important domains related to HRQOL including frustration, embarrassment, and fears about disease outcomes. Based on these results, a preliminary questionnaire is being designed to better evaluate disease-specific EoE HRQOL issues that may be missed by standardized measures of general health.

Preliminary Validation of a Measure of Adult Eosinophilic Esophagitis Patient Reported Outcomes

90,000 inhabitants without pronounced demographic changes during the last two decades. Two EoE-experienced gastroenterologists and one pathology centre are responsible for covering the gastroenterological service of the area. No public programs for increasing awareness of EoE were implemented in this region. Since 1989 all individuals with confirmed diagnosis of EoE living in Olten County were entered prospectively into the database. Results: Forty-six patients (76% males, mean age 41±16 yrs) were diagnosed with EoE between 1989 and 2009. Ninety-four percent of patients presented with dysphagia. An average annual incidence rate of 1.88/100,000 was found (range 0-8) with a marked increase in the period from 2004 to 2009. The cumulative EoE prevalence rose up to 35.1/100,000 inhabitants in 2009. No significant change was observed for the median diagnostic delay, as it was 3 years from 1989 to 1998 and 2 years from 1999 to 2009 with age < 40 years representing a risk factor for retarded diagnosis. The number of upper endoscopies per year increased by 63% in the period from 1999 to 2009 compared to the years 1989 to 1998 which is markedly less then the increase in the incidence rate of 150% for the same periods. Conclusions: Over the last 21 years, a significant increase in EoE incidence and prevalence was found in an epidemiologically stable indicator region of Switzerland. The constant diagnostic delay, the number of newly diagnosed EoE cases that was much more pronounced than the modest increase of performed upper endoscopies, as well as the lack of EoE awareness programs in Olten County indicates a true increase in EoE incidence.