Challenges in the Diagnosis of Eosinophilic Colitis: Insights from Cases Initially diagnosed as Inflammatory Bowel Disease

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study

Eructations From Eosinophils

Consortium of Eosinophilic Gastrointestinal Disease Researchers: Advancing the Field of Eosinophilic GI Disorders Through Collaboration

Little is known about the endoscopic and histologic findings of non-esophageal eosinophilic gastrointestinal diseases (EGID). To characterize the presenting endoscopic and histologic findings in patients with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) at diagnosis and 6months after initiating the treatment. We conducted a retrospective cohort study at 6 US centers associated with the Consortium of Eosinophilic Gastrointestinal Researchers. Data abstracted included demographics, endoscopic findings, tissue eosinophil counts, and associated histologic findings at diagnosis and, when available, after initial treatment. Of 373 subjects (317 children and 56 adults), 142 had EG, 123 EGE, and 108 EC. Normal endoscopic appearance was the most common finding across all EGIDs (62% of subjects). Baseline tissue eosinophil counts were quantified in 105 (74%) EG, 36 (29%) EGE, and 80 (74%) EC subjects. The mean peak gastric eosinophil count across all sites was 87 eos/hpf for EG and 78 eos/hpf for EGE. The mean peak colonic eosinophil count for EC subjects was 76 eos/hpf (range 10-500). Of the 29% of subjects with post-treatment follow-up, most had an improvement in clinical, endoscopic, and histologic findings regardless of treatment utilized. Reductions in tissue eosinophilia correlated with improvements in clinical symptoms as well as endoscopic and histologic findings. In this large cohort, normal appearance was the most common endoscopic finding, emphasizing the importance of biopsy, regardless of endoscopic appearance. Decreased tissue eosinophilia was associated with improvement in symptoms, endoscopic, and histologic findings, showing that disease activity is reversible.

Introduction: Eosinophilic colitis (EoC) is a rare entity characterized by the presence of high eosinophilic infiltrate into the colonic wall in symptomatic patients, in the absence of known other causes of colonic eosinophilia. Recently proposed guidelines suggest 100 eosinophils per high-power-field in the ascending colon, 85 in the descending, and 65 in the sigmoid colon as diagnostic thresholds. Whereas ulcerative colitis (UC), is known to be associated with an increased risk of colorectal cancer (CRC), little is known of the association between EoC and CRC. We aimed to compare EoC patients to UC patients to assess their odds of developing CRC. Methods: Using the multi-institutional, health research network database TriNetX (Cambridge, MA), de-identified, aggregated clinical data were obtained on patients with a diagnosis of either EoC or UC. Patients with other identifiable causes of eosinophilia were excluded from the EoC cohort, including inflammatory bowel disease, food allergies, helminth infections, and other eosinophilic gastrointestinal disorders. A 1:1 propensity score matching method was used to stratify EoC and UC patients. Matched variables were age at diagnosis, sex, race, obesity, tobacco abuse, alcohol abuse, and family history of digestive tract malignancy. Odds ratios(OR) and confidence intervals (CI) were calculated for development of CRC and subsequent colonoscopies for each cohort. Results: A total of 1,310 and 195,477 EoC and UC patients were identified, respectively (Table). The higher proportion of EoC patients were female compared to UC patients (65.4% vs 54.4%), and were African American (11.9% vs 9.2%). More EoC patients reported tobacco usage (4.6% vs 2.5%) and were obese (11.8% vs 7.0%) compared to UC patients. A 1:1 matching ratio stratified 1,310 patients into each cohort. After adjusting for the aforementioned covariates, EoC patients had an OR of 1.304 (95% CI 0.828-2.054, p-value 0.2503) of developing CRC compared to UC patients (Figure). EoC patients demonstrated an OR of 0.754 (95% CI 0.583-0.976, p-value 0.0313) of undergoing subsequent surveillance colonoscopies after initial diagnosis of disease compared to UC patients. Conclusion: Patients with a diagnosis of EoC have a similar risk of developing colorectal cancer compared to UC patients. Despite this, EoC patients are less likely to undergo subsequent surveillance colonoscopy compared to UC patients. Hopefully, our data can be used for future prospective studies investigating the natural course of EoC.Figure 1.: Forest plot showing odds ratios and confidence intervals of development of colorectal cancer (CRC) and subsequent surveillance colonoscopies in EoC patients compared to UC patients Table 1. - Baseline patient characteristics of EoC (eosinophilic colitis) and UC (ulcerative colitis) patients before and after 1:1 propensity score matching Baseline Patient Characteristics Before Matching p-value After Matching p-value EoC(n=1,310) UC(n=195,477) EoC(n=1,310) UC=n1,310) Age at Diagnosis 54 +/- 17.2 51 +/- 17.6 < 0.0001 54 +/- 17.2 54 +/- 17.4 0.9451 Sex Female 857(65.4%) 106,402(54.4%) < 0.0001 857(65.4%) 865(66.1%) 0.7419 Male 453(34.6%) 89,075(45.6%) < 0.0001 453(34.6%) 445(33.9%) 0.7418 Race African American 157(11.9%) 17,934(9.2%) 0.0005 157(11.9%) 134(10.2%) 0.1527 Asian 32(2.4%) 3,583(1.8%) 0.1014 32(2.4%) 39(2.9%) 0.3997 Caucasian 980(74.8%) 145,147(74.3%) 0.6468 980(74.8%) 1,007(76.9%) 0.2178 Other/Unknown 141(10.9%) 28,813(14.7%) < 0.0001 141(10.9%) 130(10.0%) 0.6152 Other Covariates Alcohol abuse 18(1.4%) 3,241(1.7%) < 0.0001 18(1.4%) 151(11.5%) 0.8078 Family history of GI cancer 38(2.9%) 4,033(2.1%) < 0.0001 38(2.9%) 49(3.7%) 0.2818 Obesity 155(11.8%) 13,688(7.0%) 0.4222 155(11.8%) 12(0.9%) 0.2706 Tobacco use 60(4.6%) 4,807(2.5%). 0.0338 60(4.6%) 31(2.4%) 0.3931

Eosinophilic Gastrointestinal Diseases (EGIDs)

Value of Food Patch Testing in Pediatric and Adult Patients with Eosinophilic Esophagitis and Eosinophilic Colitis

Eosinophilic colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions, inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination. Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics.

Introduction:Eosinophilic gastrointestinal disease (EGID) has been reported to be of higher incidence following solid organ transplantation than the general population. We reviewed the EGID incidence following single organ intestinal transplant or multi-visceral transplants at our institution. Methods:We completed a retrospective chart review on twenty-six patients who were followed at our center after intestinal or multi-visceral transplant between the years of 2003–2016. Patients transplanted prior to age of 18 and followed at least 1 year from transplant were included. Histological criteria were used for EGID diagnoses. Eosinophil infiltration of the native gastrointestinal (GI) tract only was included and not the allograft. Comparisons were done using Fisher’s exact test and Mann-Whitney two-tailed test. Results:Of the 26 individuals followed for minimum of a year after intestinal or multi-visceral transplant, 15 (15/26, 58%) individuals were subsequently diagnosed with EGID. Twelve patients (12/26, 46%) were diagnosed with eosinophilic esophagitis (EoE), one of which also had eosinophilic gastritis (EG). One patient had EG and eosinophilic colitis (EC) and one each with EC and EG. The mean age at diagnosis of EGID was 7.56 ± 5.10 years and EGID developed on average 5.20 ± 3.59 years from transplant. There was no statistically significant difference between age at time of transplant in EGID vs non-EGID (2.35 ± 2.91 vs 4.08 ± 5.07). All (15/15) patients who developed EGID were on tacrolimus at the time of diagnosis and thirteen (13/15, 87%) underwent immunosuppression induction with anti-thymocyte globulin. Five (5/15, 33%) patients also developed food allergies post-transplant, including 2 (2/11, 18%) in the non-EGID group. Three patients (3/15, 20%) were diagnosed with PTLD prior to EGID diagnosis, while no (0/11) PTLD diagnoses occurred in the non-EGID group. Rejection occurred at a greater frequency in the EGID group than the non-EGID groups (13/14, 93% vs 7/11, 64%). Mean time from first rejection episode to developing EGID was 3.74 ± 2.74 years. Eleven (11/13, 85%) EGID patients we have data on were taking at least a partial PO diet at time of diagnosis, one each of PO formula and formula by G-Tube. Conclusion:The prevalence of EGID disorders in intestinal transplants is much higher than the general population and other single solid organ transplants. Close screening for EGID development following intestinal transplant is warranted.

W1914 Clinical Features of Eosinophilic Colitis – A Report of 7 Consecutive Cases

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.

Pediatric colonic eosinophilia represents a confounding finding with a wide differential. It is often difficult to determine which children may progress to inflammatory bowel disease (IBD), which have an eosinophilic colitis (EC), and which may have no underlying pathology. There is little guidance for the practitioner on the approach to these patients. To define the clinical presentations of colonic eosinophilia and identify factors which may aid in diagnosis we reviewed patients with colonic eosinophilia and the clinicopathologic factors associated with their diagnoses. An 8-year retrospective chart review of children whose histopathology identified colonic eosinophilia (N = 72) compared to controls with normal biopsies (N = 35). Patients with colonic eosinophilia had increased eosinophils/high-power field compared to controls (P < 0.001) and had 3 clinical phenotypes. Thirty-six percent had an inflammatory phenotype with elevated erythrocyte sedimentation rate (P < .0001), chronic inflammation on colonic biopsies (P < 0.001), and were diagnosed as having IBD. Thirty-seven percent were diagnosed as having EC, associated with male sex (P < 0.005) and peripheral eosinophilia (P = 0.041). Twenty-one percent had no significant colonic pathology. Forty-three percent of patients had >1 colonoscopy and 68% of these had change from initial diagnoses. There are 3 main phenotypes of children with colonic eosinophilia. Signs of chronic systemic inflammation raise suspicion for IBD. Peripheral eosinophilia and male sex are associated with EC. A significant percent of children with colonic eosinophilia do not have colonic disease. Eosinophils/high-power field is not reliable to differentiate etiologies. Repeat colonoscopies may be required to reach final diagnoses.

A Mysterious Case of Abdominal Pain

Introduction: While recent studies have suggested that there might be an association between eosinophilic esophagitis (EoE) and celiac disease, there is a lack of studies on non-EoE eosinophilic gastrointestinal diseases (EGIDs) and celiac disease. We sought to determine the relationship between eosinophilic gastroenteritis (EoGE) and eosinophilic colitis (EoC), and celiac disease and describe the epidemiology of individuals with EoGE and EoC with co-existent celiac disease in the United States (US), utilizing a large population-based database. Methods: We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record data from 26 major integrated US healthcare systems from 1999 to May 2017. We identified an aggregated patient cohort of eligible patients with EoGE, EoC and concomitant celiac disease between May 2012 and May 2017, based on Systematized Nomenclature Of Medicine - Clinical Terms (SNOMED-CT). We calculated the prevalence of celiac disease in EoGE and EoC, among different patient groups. Results: Of the 35,795,250 individuals in the database active between May 2012 and May 2017, we identified 1,440 and 800 patients with EoGE and EoC respectively, and 84,040 patients with celiac disease. The overall 5-year prevalence rates of EoGE, EoC and celiac disease were 4/100,000, 2.2/100,000 and 234.8/100,000 persons respectively. 50 patients with EoGE also had concomitant celiac disease with the overall prevalence of celiac disease in EoGE being 3.5% (Figure 1) with an odds ratio (OR) of 15.37 (95% CI: 11.60-20.39, p < 0.0001) compared to individuals without eosinophilic gastrointestinal diseases. 30 patients with EoC also had concomitant celiac disease with the overall prevalence of celiac disease in EoC being 3.7% (OR 16.03; 95% CI: 11.13-23.08, p < 0.0001). The prevalence of celiac disease was higher in females vs males in EoGE (OR 1.11; 95% CI: 0.62-1.97, p=0.7310). Celiac disease presented predominantly in the Caucasian population in both EoGE (80%) and EoC (100%).Figure: Prevalence (%) of celiac disease in Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC).Conclusion: In this large population-based study, we found that the estimated 2012-2017 prevalence rates of celiac disease in EoGE and EoC are 3.5% and 3.7% respectively. This is one of the first large epidemiology studies that has demonstrated a significant association between celiac disease and non-EoE EGIDs. Further studies are needed to understand the mechanism of association between these disorders.

Eosinophilic gastrointestinal diseases make a name for themselves: A new consensus statement with updated nomenclature