C Ariken et al. JPGN Reports: February 2021 – Volume 2 – Issue 1 – p e037 February 2021: Full Link —Sudden Chest Pain Due to Esophageal Intramural Dissection
A Straumann et al. Gastroenterology 2020; Free Full Text Link: Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis
Methods: Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given budesonide orodispersible tablet (BOT) 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks
- At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo)
- Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment
In the discussion, the authors state that “we recommend monitoring symptoms and signs of adrenal insufficiency when administrating topical-acting corticosteroids over prolonged time periods, in particular in children and when using higher dosages.”
My take (from discussion): “EoE requires a proper long-term anti-inflammatory therapy because, without active treatment, the vast majority of patients experience a relapse within the first 100 days after cessation of the medication.”
Related blog posts:
- Phase 3 Trial of Budesonide for EoE
- New 2020 Eosinophilic Esophagitis Guidelines | gutsandgrowth
- Head-to-Head: Budesonide vs Fluticasone for Eosinophilic Esophagitis | gutsandgrowth
- Grading Treatment Response in Eosinophilic Esophagitis | gutsandgrowth
- Orodispensable Budesonide Tablets for EoE
- Surprising Findings in Prospective Budesonide-Eosinophilic Esophagitis Study
- What Happens When Topical Steroids are Stopped in EoE
A recent study shows similar clinical, endoscopic and histologic findings between eosinophilic esophagitis (EoE) and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) (Aliment Pharmacol There 2014; 39: 603-08 -thanks to Seth Marcus for this reference).
The authors used two databases: one from Walter Reed and one from the Swiss EoE database. All of these patients were >/=18 years. Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least 6-weeks of PPI treatment.
Demographics: 63 EoE patients, 40 PPI-REE, mean age 40 years (75% male, 89% Caucasian).
- Similar dysphagia 97% vs. 100% (in EoE and of PPI-REE cohorts)
- Similar food impaction 43% vs. 35% (in EoE and of PPI-REE cohorts)
- Similar heartburn 33% vs. 32% (in EoE and of PPI-REE cohorts)
- Similar duration of symptoms: 6.0 years vs 5.8 years (in EoE and of PPI-REE cohorts)
- Similar endoscopic findings too: rings 68% in both groups, furrows 70% in both groups, strictures 49% vs 30% (in EoE and of PPI-REE cohorts)
- Similar histology: proximal esophagus 39 vs 38 eos/hpf and distal esophagus 50 vs 43 eos/hpf
Take-home message: EoE and PPI-REE are very similar in presentation and indistinguishable without a PPI trial.
Related blog posts:
- Nexium versus Fluticasone for EoE | gutsandgrowth
- EoE -Journal Club (Part 1) | gutsandgrowth
- EoE: Drugs, Diets, Dilatation and PPI-REE | gutsandgrowth
In patients with eosinophilic esophagitis (EoE), the development of fibrosis due to ongoing inflammation is one of the concerns as this can lead to more difficulty with swallowing, food impactions, a smaller caliber esophagus, and stricturing. A recent report highlights a way to measure esophageal distensibility and its correlation with disease severity (Clin Gastroenterol Hepatol 2013; 11: 1101-7).
This report describes the evaluation of 70 patients with EoE (ages 18-68 years with median of 38 years`, 50 men) who underwent endoscopy along with high-resolution impedance planimetry. The average followup was 9.2 months. The functioning luminal imaging probe (FLIP) system was used after the endoscopy by placing a catheter transorally. The catheter had 16 ring electrodes spaced 5-mm apart in the 8-cm measured segment. The FLIP distal recording began 3 cm proximal to the esophageal gastric junction. Esophageal cross-sectional areas were measured during 2-mL stepwise distentions and increasing to a maximum of 40 mL.
Patient EoE Clinical Features at baseline:
- 26 patients had a history of food impaction
- 37 patients had dysphagia
- 5 patients had chest pain
- 2 patients had heartburn
- Ringed esophagus: 9 (13%) had severe endoscopic findings, 17 (24%) had moderate endoscopic findings, 40 (57%) had mild endoscopic findings
- Primary treatment: PPI treatment (78%), Topical steroids (10%), diet 4 (6%)
- Patients with food impaction had significantly lower distensibility plateau (DP) than those with solid dysphagia alone (see manuscript Figure 1).
- Mean DP in food impaction 113 mm2 compared with 229 mm2 for those without a history of food impaction
- The severity of mucosal eosinophilia did not correlate with risk for food impaction, distensibility, or requirement for dilatation.
In many ways, the findings are completely obvious. If an individuals esophagus is less distensible, it makes sense that food could get stuck. However, the article highlights a novel way of assessing esophageal distensibility in this population. While the study did not identify higher mucosal eosinophilia as a marker of distensibility, this may be a precursor to future problems. In the discussion, the authors note that a 12.5 mm barium tablet test correlates with a 125-mm2 threshold. Thus, their data suggest a corresponding diameter of 17 mm as a prerequisite to avoid food impactions.
Bottomline: this study identifies a new way to assess the risk for food impactions in EoE by measuring esophageal distensibility.
Related blog entries:
- GUIDELINES FOR EOSINOPHILIC ESOPHAGITIS | GUTSANDGROWTH
- EoE –Journal Club (Part 1) | gutsandgrowth
- EoE –Journal Club (Part 2) | gutsandgrowth
- Natural History of EoE –Journal Club (Part 3) | gutsandgrowth
- CHOOSING TOPICAL THERAPY FOR EOE | GUTSANDGROWTH
- EOSINOPHILIC ESOPHAGITIS –SIX FOOD GROUP DIET | GUTSANDGROWTH
- LOOK OF IMPROVEMENT ON AN EOE DIET | GUTSANDGROWTH
- STRING TEST | GUTSANDGROWTH
- LOOKING BETTER OR FEELING BETTER IN EOE? | GUTSANDGROWTH
- THE UNDISCOVERED COUNTRY | GUTSANDGROWTH
A recent study confirms that an empiric ‘6-food elimination diet’ (SFED) works in adults with eosinophilic esophagitis (EoE) as well as it has been shown to work in kids (J Allergy Clin Immunol 2013; 131: 797-804)). Thanks to Seth Marcus for this reference.
This Spanish study recruited 67 consecutive adult patients (17-60 years) who were treated with an exclusive diet which eliminated milk (avoided goat’s milk too), wheat/cereals (avoided rice and corn too), eggs, fish/seafood, legumes/peanuts, and soy for 6 weeks. Subsequent rechallenge followed with repeated endoscopies every 6 weeks. A food was considered a trigger for EoE if eosinophilic infiltrate ≥ 15 Eos/hpf after reintroduction.
Prior to reintroduction, 73% (n=49) responded to SFED with peak Eos < 15/hpf. Among responders, 37 patients achieved a complete response with Eos 0-5/hpf. Subsquently rechallenges were instituted and 42 patients completed this part of the study. A single food was identified in 36%, 2 food triggers in 31%, the remainder had at least 3 food triggers. Cow’s milk was the most common food trigger, in 62%, followed by wheat (29%), eggs (26%), and legumes (24%).
Allergy testing (ImmunoCap IgE-based testing, and skin prick testing) showed no concordance with food reintroduction challenge results. All patients maintained on avoidance of offending foods maintained remission for up to 3 years.
In the general scheme of food reintroduction, it is interesting that the authors often tested for wheat and milk first. Also, the Table 1 listed numerous characteristics of responders and nonresponders and none of these had a significant predictive effect. This table listed symptoms including dysphagia, vomiting and pain, caliber of esophagus, mucosal appearance, atopic history, atopic family history, and eosinophil counts.
Related blog entries:
PPI-REE or proton pump inhibitor-responsive esophageal eosinophilia remains a problematic issue for our eosinophilic esophagitis (EoE) patients. PPI-REE and the 3 D’s (Drugs, diet, and dilatation) have been reviewed recently (Clin Gastroenterol Hepatol 2012; 10: 1066-78).
The issues with PPI-REE that are problematic:
- If a patient with suspected EoE is pretreated with a PPI and they do not have eosinophils present at the time of endoscopy then a diagnosis of PPI-REE cannot be established.
- If patients are not pretreated, then determining that they have PPI-REE compared with typical EoE, requires repeat endoscopy. Furthermore, response to PPI may be transient and/or natural variation in EoE could make definitive diagnosis of PPI-REE quite difficult.
- If a patient presents with classic-appearing EoE, choosing to treat with a PPI is difficult as the response rate is much lower than with either dietary therapy or drug therapy. In addition, many symptomatic patients may have been treated to some extent with a PPI. Do they warrant repeat treatment and repeat endoscopy prior to using more typical treatment for EoE?
Beyond this topic, this review covers the recent consensus guidelines and the typical treatments: diets, drugs, and dilatation.
With regard to dilatation, the author notes that it may be safer than previously believed. Furthermore, in a recent trial, 81% were symptom free at 3 months and 46% were symptom free at 1 year. Despite better safety results, 74% of patients in one study complained of retrosternal pain after in endoscopy (moderate in 21% and severe in 17%).
With regard to drug or dietary therapy, the author recommends checking on the effectiveness after 6-8 weeks with a repeat endoscopy. Until better tools for assessing response to therapy become available, endoscopy remains the only accurate way to determine if treatment is working.
Related blog entries:
A study from Philadelphia/CHOP offers more insight into food selection diets for eosinophilic esophagitis (EoE) (Spergel JM, et al, J Allergy Clin Immunol 2012; 130: 461-7) –thanks to Seth Marcus for forwarding this article to my attention.
For this study, the authors examined their database of 1187 patients. While the data was collected prospectively, this was a retrospective study. Of this 1187, the authors excluded patients with proton pump inhibitor-responsive EoE (n=191) along with patients with more extensive eosinophilic GI diseases (n=55).
Among the remaining 941, the male-to-female ratio was 2.8:1 and the average age was 6.4 years. Concurrent atopic disorders were common: 64% had rhinitis, 50% had asthma, and 24% had atopic dermatitis. Only 18% had no atopic disorders.
The actual number for the study though was 319. Among the 941 noted above, 148 were receiving medications (n=130 for topical steroids), and causative foods were not identified in 474. In some of these patients, families were content to stick with a multiple food elimination without determining with certainty which foods were truly necessary.
In less than 5% of patients, a strict elemental diet was used. In this group, the population was younger (average 2.8 years). Biopsy improvement was noted in “upward of 98%.”
- Elimination of foods based on combined skin prick tests (SPT)/atopy patch tests (APT) had an identical response to the six food group diet –53%. The allergy testing group had less eliminated foods (average 3.2 foods) compared with 8 food groups in SFED.
- Elimination of milk with SPT/APT testing resulted in 77% response. Authors note that there was a “particularly high false-negative rate (34%)” with milk testing (SPT/APT).
- Elimination of top 8 allergens: milk, soy, egg, wheat, and meats [chicken, turkey, pork, beef] had an identical response of 77%.
- Elimination of milk, egg, and wheat had a success rate of 48%. Milk only elimination had a 30% response rate.
- Most common foods by biopsy: milk (35%), egg (13%), wheat (12%), soy (9%), corn (6%)
- Most common foods by symptoms: milk (19%), egg (11%), wheat (9%), soy (10%), beef (8%)
- IgE-mediated foods: milk (10%), egg (17%), soy (4%), peanut (22%)
Additional useful information in the addendum of methods notes their technique for APT testing (which is not standardized across centers). The authors use 2 g of dry foods in 2 mL of isotonic saline solution for most foods; for milk, they use 3 g of powdered milk with 1 mL of isotonic saline. Then these mixtures are placed in aluminum cups (6- or 12-mm Finn chambers on Scanpore). These cups are placed on patient’s backs and removed at 48 hours and read at 72 hours.
In addition, for each food, their tables list predictive values (positive predictive value, negative predictive value, sensitivity, and specificity) for SPTs, and for APTs. Overall, the predictive values are quite variable and much different from the general population. For example, in the general population, the negative predictive value is essentially 100% for combination of SPT/APT.
Previous related blog entries: