Tag Archives: dysphagia

Natural History of EoE -Journal Club (Part 3)

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This posting reviews the final article for our eosinophilic esophagitis (EoE) journal club: Aliment Pharmacol Ther 2013; 37: 114-21.

Design: Cross-sectional study of adult EoE patients (≥ 18 years) who were diagnosed at the Children’s Hospital of Philadelphia.  Patients underwent dysphagia questionnaire, Mayo Dysphagia Questionnaire (MDQ-30), and a patient assessment of upper gastrointestinal disorders quality of life questionnaire (PAGI-QOL). Of 140 eligible patients, 53 completed the questionnaires, 66 were unable to be contacted, and 21 refused to participate.

The MDQ-30 has been validated as a tool for esophageal strictures of 15 mm or smaller.  It has not been confirmed as a EoE dysphagia tool.

Diagnosis: According to the authors, a diagnosis of EoE required a >20 eosinohils/hpf after a 2-month therapeutic trial of proton pump inhibitors.

Results:

  • Mean age 20.5 years.  98% were caucasian and 75% were male.  15% had a history of esophageal dilatation.
  • 6/53 had positive dysphagia scores.  However, 18/47 with negative scores reported ongoing difficulty swallowing.
  • 26 (49.1%) of subjects were receiving proton pump inhibitor therapy and 40 (76%) were following allergy-directed dietary elimination.  Most common allergy in this cohort was dairy (49%) followed by peanuts/tree nuts (23%), eggs (9%), wheat (9%), soy (8%), and seafood (2%).**
  • Overall, dietary QOL scores, but not overall QOL scores, were adversely affected by ongoing EoE.

**With regard to dietary therapy, there is a significant discrepancy in reported allergy avoidance in this cohort compared with some previous data published by this center. For example, Liacouras et al (Clin Gastro Hepatol 2006; 3: 1198) reported a  98% improvement with diet treatment (n=351) (2/3rds were treated with elemental diet, mostly NG, with food reintroduction).  Their protocol included rebiopsy after introduction of last new food.  75/242 responded to elimination of specific foods.  Overall pattern of food avoidance after biopsy: milk 45%, eggs 45%, soy 38%, corn 38%, wheat 30%, beef 30%, chicken 20%, potato /oats/peanuts 15%, turkey/barley 11%, pork 8%, rice 5%, green beans 3%, apples /pineapple 1%.*  The reported allergens in this study match up much more closely to a highly-selected group of patients that was more recently reported from their database and is reviewed separately (Picking the right diet for EoE | gutsandgrowth).  In this group, the authors stated that the most common foods by biopsy were the following: milk (35%), egg (13%), wheat (12%), soy (9%), corn (6%).

Study limitations:

  1. Small number of patients
  2. Low response rate/responder bias
  3. Retrospective cross-sectional study -does not provide longitudinal data
  4. Young age of subjects
  5. MDQ-30 not validated for dysphagia in EoE
  6. Tertiary children’s hospital with research focus on EoE
  7. No recent endoscopies in research cohort

Take-home message: EoE is a chronic disease with “little resolution of either symptoms or oesophageal eosinophilia without ongoing treatment.”

 

Stopping reflux with magnets

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Gastroesophageal reflux disease (GERD) can be treated by bolstering the lower esophageal sphincter with a surgically-implanted bracelet of powerful magnets (NEJM 2013; 368: 719-27).

In a prospective study, 100 patients with GERD were enrolled in this study.  The study was conducted in 13 centers in the U.S. and 1 in the Netherlands.  It was designed by Torax Medical.  There was no control group. The primary outcome was normalization of esophageal acid exposure or a 50% greater reduction in exposure at 1 year.

Patient selection:

  • Inclusion criteria: 18-75 years with at least 6-month history of GERD and partial response to proton pump inhibitor treatment.  All patients had to have abnormal pH probe studies at baseline.
  • Exclusion criteria: large hiatal hernia, grade C or D esophagitis (Los Angeles classification), BMI >35, Barrett’s esophagus, motility disorder, dysphagia more than three times a week, or allergy to implant components.

Results:

  • Primary outcome was achieved in 64% of patients.
  • Secondary outcomes: a reduction of proton-pump inhibitor (PPI) use of 50% or more was achieved in 93%.  In fact, at 3 years, 87% had completely eliminated the use of PPIs. Quality of life scores improved in 92%.
  • Adverse effects: most common was dysphagia (68% postop, 11% at 1 year, 4% at 3 years).  This often resolved after esophageal dilatation.
  • Six patients had the device removed.

The bracelet of beads contained sealed magnetic neodymium iron boride.  Each bead is connected by a small wire to the next.  The small wires allow for expansion of the bracelet. It is also designed to avoid compression of the esophagus as the beads can rest against each other.  In addition, the beads separate with the transport of food or if increased intragastric pressure (eg. belch or vomit).

The median time for the procedure of laparascopic placement was 36 minutes. This study brings the worldwide clinical experience to 497 magnetic implants.  To date, there have been no reported erosions or migrations.

Related blog entries:

The undiscovered country

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The title of this blog is derived from a Star Trek movie.  I think that when we see patients with eosinophilic esophagitis that we are often seeing something new and poorly characterized.

Despite so many unanswered questions, particularly on an individual basis, this topic has seen a lot of interest and there are many advances in both bedside and basic research.  The review article  (Allergy 2012; DOI: 10: 10.1111/j.1398-9995.2012.02787.x) focuses on many of the similarities and differences between pediatric and adult patients.  Is it the same disease? (Probably yes)

With regard to medical history, the article reminds clinicians to ask about coping strategies:

  • do you wash food down with liquid?
  • are you the last one to finish your food?
  • do you chew your food a long time?
  • do you avoid foods like meats or breads?

Clinical features –main difference is greater presentation variety in children.  Adults almost always have long-standing dysphagia.  In pediatrics, painful symptoms, reflux symptoms, and feeding refusal are often seen in early stages.  In both populations, other atopic diseases are very common.

Immunopathogenesis (same in pediatrics and adults):  Th2-type inflammatory response; not just eosinophils but also IL-5-expressing T-cells, B cells, and IgE-bearing mast cells.  A break-down of all the types of quantified cells from a large number of studies is detailed (Table 2).

Allergic profile –main difference is much higher aeroallergen sensitization in adolescent & adult patients than in pediatric patients.  In children, top four allergens: milk, wheat, egg, and soy.  In older patients/adults, nuts are frequent food allergens.

Treatment strategies –basic question of whether to treat for symptomatic relief or histologic response is still debated.  Three goals of treatment are the same:

  • improve quality of life
  • reduce the risk of severe esophageal injury
  • prevent esophageal damage

3 D’s of treatment drugs, diet, dilatation:

Drugs: topical steroids (fluticasone, budesonide) are effective in ~50% of children & these agents may reverse subepithelial fibrosis, PPIs -small percentage have EoE PPI-responsive disease, & systemic steroids.  Lower doses of budesonide may be effective as maintenance treatment (0.25mg BID).  Interestingly, infliximab has not been effective clinically or histologically despite the high amounts of TNF.  Azathioprine (or 6-MP) was effective in three steroid-dependent patients in a pilot study.

Diet –review does not cover new territory (see previous blog: Eosinophilic Esophagitis -Six Food Group Diet).  States that elemental diets are not practical in adults.  Discusses the fact that food allergy identification is difficult & remains a pressing research need.

Dilatation –can provide long-lasting symptom relief.  Dilatation is infrequently utilized in pediatrics and virtually never in absence of other therapies.

On a side note, in my training I was taught that there were 3D’s to treating every patient: diet, drugs, and demeanor — a good attitude goes a long way, particularly in an uncertain world.

Additional references:

  • -Gastroenterology 2011; 141: 1593.  anti-IL-5.  partially effective for EoE.
  • -JPGN 2010; 51: 723. n=91.  Incidental gastric eosinophils does not predict a worse response to fluticasone then isolated EoE.
  • -Clin Gastro & Hepatology 2011; 9: 400 (editorial 370). Budesonide at dose of 0.25mg BID was partially effective in adult cohort of n=28.
  • -Aceves SS et al. Allergy 2010; 65: 109-116. 3 month course of budesonide can lead to resolution of esophageal remodeling. Lamina propria fibrosis resolution correlates with response to topical steroids. Examined effect on lamina propria after 3 months of Rx.
  • -Gastroenterology 2010; 139: 1526. n=36. (summary pg 1429) 15 day course of budesonide (1mg BID). 13/18 in Rx group had improved dysphagia, 72% wiht histologic remission, 92% reduction in eosinophil count. Did not seem to matter if “allergic” or not. 3 pts developed mild candida.
  • -Gastroenterology 2010; 139: 418. Randomized placebo study showed effectiveness.n=15 Rx (n=9 placebo). 87% of Rx group responded.  2ml of water with 0.5gm pulmicort and mixed it with 4-5 packets of splenda.
  • -JPGN 2007; 45: 281/370/319. Review/research symposium/subepithelial fibrosis associated with EoE & dysphagia.
  • -JPGN 2007; 45: 22-31. Th2 Immunity w Eotaxin-3/ C-C chemokine receptor in EoE.
  • -Gastroenterology 2006; 131: 1381-1391. Randomized double-blind, placebo-controlled trial of fluticasone for EoE: 880mcg divided bid; n=21 Rx, n=15 placebo. 50% (vs 9% controls) achieved histologic remission; Rx more effective in those w/o detectable food allergies. 67% (vs. 27% controls) resolution of vomiting.
  • -Clin Gastro & Hep 2007; 5: xxiv. EoE causing Boerhaave’s syndrome (spontaneous rupture)
  • INCREASED FRAGILITY: -Gastrointest Endosc 2003; 57: 407-12. -Clin Gastro Hepatolo 2003; 1: 433-37.
  • -Clin Gastro & Hep 2006; 4: 1328. absolute eosinophilia (AEC 440 vs 140 controls), eosinophil-derived neurotoxin, and eotaxin-3 act as biomarkers of EE activity.
  • -Gastroenterology2006; 131: 2018 (-J Clin Invest 2006; 116: 536-547. ) Eostaxin-3/EcE transcript signature.
  • -J Pediatr 2005; 147: 540 Picture of ringed esophagitis.
  • -JPGN 2004; 39: S8 [abstract 0005]. CHOP experience in 250 pts. NG elemental diet was most effective. ~6% of pts presenting with GER. Strict avoidance of allergens needed.