Association of eosinophilic esophagitis with autoimmune and connective tissue disorders, and the impact on treatment response.

Eosinophilic esophagitis (EoE) has been associated with autoimmune (AI) and connective tissue disorders (CTDs), but clinical correlates and treatment response to topical corticosteroids (tCS) for patients with both conditions are not well known. We aimed to determine the prevalence and clinical features of AI/CTDs in EoE patients, and assess the response to tCS. In this retrospective cohort study of adults and children newly diagnosed with EoE in the University of North Carolina EoE Clinicopathologic database, we extracted clinical characteristics and treatment response data. We compared EoE patients with and without AI/CTDs, identified independently associated factors, and explored treatment responses. Of 1029 EoE patients, 61 (5.9%) had an AI/CTDs. The most common AI/CTDs were psoriasis/psoriatic arthritis (P/PA) (1.7%), Hashimoto's (1.2%), and rheumatoid arthritis (RA) (1%). Compared to those without AI/CTDs, AI/CTDs patients were older (35 vs. 28 years, P = 0.004), more likely to be female (51% vs. 30%, P = 0.001), have insurance (93% vs. 78%, P = 0.004) and a longer symptom duration prior to EoE diagnosis (10 vs. 7 years, P = 0.02). Older age, female sex, having insurance, and having allergic rhinitis were independently associated with AI/CTDs. AI/CTD patients with EoE were less likely to have a symptom response (47% vs. 79%, P = 0.003). Overlap between EoE and AI/CTDs was uncommon, seen in approximately 6%, with P/PA, Hashimoto's, and RA being most frequent. In conclusion, older age, female sex, having insurance, and allergic rhinitis were independently associated with AI/CTDs. EoE patients with AI/CTDs had less symptom response, with trendtowards lower endoscopic and histologic responses, to tCS therapy.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Drivers of Variation in Diagnosis and Management of Eosinophilic Esophagitis: A Survey of Pediatric Gastroenterologists.

BACKGROUND: Widespread variation in the diagnosis and treatment of eosinophilic esophagitis (EoE) has previously been reported among adult gastroenterologists; however, variation in EoE practice in among pediatric populations is poorly characterized. The study objectives were to describe guideline adherence and understand reasons for variation in EoE practice among pediatric gastroenterologists following publication of the updated 2018 international EoE guidelines. METHODS: We developed and administered a 28-item survey to pediatric gastroenterologists via an email listserv using the PEDGI Bulletin Board from 03/2019 to 04/2019. The survey was developed using evidence-based review, expert validation, and cognitive interviews. Survey domains included respondent knowledge of and adherence to published guidelines, diagnostic and management approach and rationale, and participant demographics. Analysis included descriptive statistics and tests for association. RESULTS: A total of 288 pediatric gastroenterologists completed the survey, most of whom practiced in an academic center (73%). More than half (63%) reported knowledge of the 2018 updated guidelines; however, only 52% agreed with them and 50% reported adherence. Respondents who reported not agreeing with updated guidelines cited concerns regarding increasing number of endoscopies (72%), misdiagnosing eosinophilia from reflux (56%), and insufficient data (23%). The most common drivers of decision making with respect to therapy choice were patient/family preference, evidence/guidelines, and symptom burden. CONCLUSIONS: Many physicians are not adherent to current guidelines for reasons which include lack of knowledge of updated guidelines and concern regarding the strength of the supporting evidence. This study elucidates several areas to enhance education regarding these guidelines to promote widespread adherence.

Use of Patient-Reported Outcomes Measurement Information System Pediatric Measures as Clinical Trial Endpoints: Experience from a Multicenter Pragmatic Trial in Children with Crohn's Disease.

OBJECTIVES: To evaluate whether Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric patient-reported outcome (PRO) measures can serve as valid endpoints in a clinical trial of a chronic pediatric illness. STUDY DESIGN: We evaluated the responsiveness of PROMIS pediatric measures collected through the Clinical Outcomes of Methotrexate Binary Therapy in Practice (COMBINE) trial, a multicenter, randomized, double-blind, placebo-controlled, pragmatic clinical trial in pediatric patients with Crohn's disease (CD). We examined the relationships between changes in PROMIS pediatric measures and changes in disease activity by evaluating PRO score changes among patients who did and patients who did not experience improvement in disease activity. RESULTS: Participants included 266 children and adolescents with CD from a total of 35 institutions. Over the course of follow-up, participants showed improvement in most PRO domains, with the largest effect sizes observed for the clinically improved group. Patients who maintained steroid-free remission showed significantly lower PRO scores for the Pain Interference, Fatigue, and inflammatory bowel disease (IBD) Symptoms domains and higher scores for the Positive Affect domain. CONCLUSIONS: This study demonstrates the responsiveness of the PROMIS pediatric measures of Fatigue and Pain Interference as study endpoints in a large, multicenter pragmatic trial in pediatric CD, extending a growing body of research supporting the use of PROMIS pediatric measures as reliable PRO endpoints for clinical trials.

Psychiatric Comorbidities Are Highly Prevalent in Nonesophageal Eosinophilic Gastrointestinal Diseases.

BACKGROUND & AIMS: The prevalence of psychiatric comorbidity in nonesophageal eosinophilic gastrointestinal disorders (EGIDs) has not been studied. We aimed to ascertain the prevalence of psychiatric diagnoses and psychiatric medication use in children, adolescents, and adults with EGIDs and to assess whether psychiatric comorbidity affects clinical presentation. METHODS: This was a retrospective cohort study of newly diagnosed patients with a nonesophageal EGID at the University of North Carolina from 2008 to 2020. Psychiatric diagnoses and medications were extracted from medical records. We compared the clinical and demographic features of EGID patients with and without psychiatric diagnoses. RESULTS: Of 79 patients (mean 23.3 years of age, 53% male, 78% White) with a nonesophageal EGID diagnosis, 40 (51%) were diagnosed with a comorbid psychiatric disease. Anxiety (37%) and depression (28%) were most common. There were also 40 (51%) patients treated medically for a psychiatric diagnosis. Patients with a psychiatric diagnosis were more commonly ≥18 years of age at the time of EGID diagnosis (odds ratio [OR], 3.95, 95% confidence interval [CI], 1.20-13.02) and had endorsed symptoms of nausea (OR, 5.31; 95% CI, 1.33-21.22) and dysphagia (OR, 4.24; 95% CI, 1.18-15.26). CONCLUSION: Psychiatric diagnoses were very common in nonesophageal EGID patients with approximately 7 in 10 adults and one-third of children diagnosed. Similar proportions were found for psychiatric medication use. We also found that psychiatric illness may influence age of clinical presentation and symptoms. Providers should assess for concomitant psychiatric comorbidities in EGID patients.

Older patients with eosinophilic esophagitis have high treatment response to topical steroids.

BACKGROUND: There are few data assessing treatment response in older eosinophilic esophagitis (EoE) patients and we evaluated treatment outcomes to topical corticosteroids (tCS) in this older population. METHODS: This retrospective cohort study of the UNC EoE Clinicopathologic database included subjects with a new diagnosis of EoE treated with tCS. Histologic responses, global symptom response, and endoscopic changes were recorded. Older EoE patients (≥65 years) were compared to younger EoE patients (<65). RESULTS: We identified 467 EoE patients treated with tCS, 12 (3%) of whom were ≥65 years. Compared to those <65 years, patients ≥65 had longer symptom duration and worse endoscopy scores, but most clinical features were similar. Post-treatment peak eosinophil counts trended higher in the <65 group (25.0 vs 5.5; p = 0.07). Histological response was greater in the ≥65 population at <15 eos/hpf (92% vs 57%; p = 0.02), ≤6 eos/hpf (83% vs 50%; p = 0.02), and <1 eos/hpf (58% vs 29%; p = 0.03). Older age was independently associated with increased odds of histologic response (adjusted OR 8.48, 95% CI: 1.08-66.4). CONCLUSIONS: EoE patients ≥65 years had a higher likelihood of responding to tCS therapy, suggesting they should be studied more closely and included in future trials.

Nutritional Therapy in Very Early-Onset Inflammatory Bowel Disease: A Case Report.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract caused by a dysregulated immune response to the fecal microbiota. Very early-onset inflammatory bowel disease (VEO-IBD) refers to a subgroup of pediatric patients with IBD diagnosed before 6 years of age. This subgroup is often characterized by increased severity, aggressive progression, strong family history of IBD, and often poor response to conventional treatments. Nutritional therapies have been utilized to treat IBD, but their role in VEO-IBD is unclear. Disease behavior in VEO-IBD is often different from disease in adolescents and adults, as it is often restricted to the colon and refractory to standard medical therapies. Up to 25% of VEO-IBD patients have an identified underlying immunodeficiency, which may impact response to therapy. While specific mutations in interleukin 10 (IL-10), the IL-10 receptor (IL-10R), and mutations in NCF2, XIAP, LRBA, and TTC7 have been identified in VEO-IBD, polymorphisms in these genes are also associated with increased risk of developing IBD in adolescence or adulthood. We describe two cases in which infants presenting with VEO-IBD achieved clinical remission using exclusive enteral nutrition, a formula-based diet which has been shown to induce remission in older children with active Crohn's disease.