In 2011, leaders of regional endoscopy units in Northern Denmark reached a consensus on a protocol to take eight biopsy samples in dysphagia patients (four biopsies from 4 cm and 14 cm above the esophagogastric junction-“4-14-4 rule”) regardless of the macroscopic appearance.
Key finding: Thenumber of patients with esophageal eosinophilia detected per year increased 50-foldafter the protocol was implemented in 2011 (median of 1 [interquartile range 0-3] vs. 52 [47-56]; P < 0.001), and the number of biopsy samples per patient doubled (median 4 [4-5] vs. 8 [6-9]; P < 0.04). In total, there were 309 with esophageal eosinophilia identified from 2007-2017.
My take: This study provides more data that more biopsies help identify more cases of eosinophilic esophagitis.
Related blog posts:
Best Approach for Identifying Eosinophilic Esophagitis Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens. Also, prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful. Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.
Using the Inform Diagnostics database, which is a national electronic repository of histopathologic records from patients distributed throughout the entire United States, the authors performed a case-control study among 302,061 patients undergoing bidirectional endoscopy on the same day.
The database contained 3860 ulcerative colitis (UC) patients, 3330 Crohn’s disease (CD) patients, 1476 patients with indeterminate colitis with respect to UC or CD, and 5296 MC (microscopic colitis) patients.
EoE was less common in the overall IBD, CD, and MC case populations than the control population. Adjusted odds ratios (compared to control) :
EoE and IBD aOR 0.64
EoE and Crohn’s aOR 0.41
EoE and UC aOR 0.97
EoE and Indeterminate Colitis aOR 0.29
EoE and MC aOR 0.68
My take: (partly from authors) “Unexpectedly, the present analysis revealed statistically significant inverse relationships between EoE and CD or MC, but not UC.” Because endoscopy is often undertaken in those with a suspicion of IBD, EoE can be identified in the IBD population surreptiously; however, its frequency is likely less than in the general population.
This study analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. 20 of the 86 initial subjects (from the 16 week induction study) did not complete the full 52-week duration of the open label extension
Overall, 42 of 66 (64%) subjects had a peak eosinophil count <15 at 52 weeks
In the initially-treated group, 29/57 (51%) had peak eosinophil count <15 at 16 weeks
20/29 maintained a eosinophil count <15 at 52 weeks; 3 had an eosinophil count of 15 or greater at 52 weeks. Thus, 20/23 (87%) with data at 52 weeks maintained response.
In the initially-treated group, 28/57 (49%) had a peak eosinophil count of 15 or greater at 16 weeks
10/28 (36%) had a peak eosinophil count <15 at 52 weeks and 12 continued with an eosinophil count of 15 or greater at 52 weeks. Thus, 10/22 (45%) acquired a response after the induction period.
In the placebo induction group (n=29), none had a peak eosinophil count <15 at week 16
12/29 (43%) had a peak eosinophil count <15 at 52 weeks during open-label treatment; 9 continued with an eosinophil count of 15 or greater at 52 weeks. Thus, 12/21 (57%) developed a response without an induction treatment.
In addition to the improvements in eosinophil count, the authors identified clinical, endoscopic, and histologic improvement. “RPC4046 was well tolerated with little immunogenicity elicited in the LTE period.” Overall, the majority of treatment related adverse events were mild or moderate in severity and “no significant safety concerns.”
My take: This study shows that RPC4046 may emerge as a useful treatment for EoE.
The FLIP “measures luminal cross sectional area (CSA) and pressure in the esophagus using impedance planimetry and serves as an adjunct to existing esophageal investigative tests. A distensible balloon encasing a catheter with multiple pairs of impedance electrodes is used, and the balloon is distended with fluid of known conductivity and volume.”
FLIP can be done at time of endoscopy.
Distensibility index (DI). This is the ratio of EGJ cross sectional area to intraballoon pressure is generally considered the most useful FLIP metric. Normal DI values in adults range from 3.1 to 9.0 m3/mm Hg. Lower values indicated reduced EGJ opening.
FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms.
FLIP can be used to assess fibrostenotic remodeling of the esophagus in eosinophilic esophagitis.
Lumen diameter measured using FLIP in complex strictures can potentially guide management.
This review has several helpful figures to illustrate the type of visual data available. It also provides a standard protocol for using FLIP. The current limitations for FLIP include the lack of real-time software analysis of the data which hinders reporting, and limited data supporting use.
Background: AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells.
Methods: In this phase 2 trial, the authors randomly assigned adults (n=65) who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo
The mean percentage change in gastrointestinal eosinophil count was −86% in the combined AK002 group, as compared with 9% in the placebo group
Treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo
The authors note that AK002 “also resulted in alleviation of dysphagia in patients with a history of concomitant eosinophilic esophagitis.”
Limitations: Small study and 10% developed antibodies to drug
My take: Larger phase 3 studies with AK002 are underway (NCT04322604 & NCT04322708). AK002 looks promising for eosinophilic gastrointestinal diseases.
One aspect about this review that I liked was the dietary step-up –step-down therapy figure:
Reference: J Molina-Infante et al. J Allergy and Clincal Immunology. DOI:https://doi.org/10.1016/j.jaci.2017.08.038Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 studyResults: A TFGED (2-food) achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs (4-food) and SFGEDs (6-food) were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%.
This guideline was developed through a collaboration between AGA and the Joint Task Force for Allergy-Immunology Practice Parameters, which comprises the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. This guideline is jointly published in Gastroenterology and Annals of Allergy, Asthma and Immunology.
A recent double-blind pilot study (n=20) (JM Spegel et al. Clin Gastroenterol Hepatol 2020; 18: 328-36) explored the use of epicutaneous immunotherapy (EPIT) in children with milk-induced eosinophilic esophagitis (EoE). 15 children received active treatment with a “Viaskin” milk allergen extract patch and 5 children received a placebo.
The premise of EPIT for EoE has been based on animal models (mouse & piglet) which have shown that epicutaneous desensitization to peanuts has been successful in preventing development of EoE.
The design of the study involved EPIT during a 9 month milk-free period followed by a milk-containing diet for 2 months. Biopsies were taken and then there was an additional 11 month open-label phase in which all patients received EPIT.
No significant differences in mean eos/hpf in the two groups: 50 vs 48 in EPIT compared to placebo respectively.
There were 9 of 19 (47%) had a significant drop in eosinophil count with less than 15 eos/hpf at the end of the open-label phase.
Overall, adverse events were similar in both groups, though the EPIT group had more frequent GI adverse events than the placebo group (67% vs. 40%)
My take: The primary and secondary endpoints were not reached in this study. However, based on the open-label phase response, further studies are warranted.