Tag Archives: Digestive Disorders

How To Stay Informed

Thanks for following along with the diagnosis and treatment of eosinophilic esophagitis (EoE)–a condition that during my fellowship training in allergy wasn’t even recognized as a cause of abdominal pain. 

Treatment options for EoE are currently:

  • Corticosteroids–both oral and inhaled
  • Dietary avoidance of known allergic triggers, including but not limited to foods 
  • Use of PPIs such as Nexium & Protonix
  •  Treatment principles focus on reducing symptoms and eosinophil counts while, importantly, protecting and preserving quality of life.
  • Maintaining diet and nutrition which is harder than it looks! Don’t forget that restoring growth parameters are also essential for adults as well as in children.
Tastes Great, but NOT less filling!

As with all diseases, treatment is updated constantly, and new recommendations emerge.   As with many inflammatory conditions, steroids work great, but are NOT less filling.  Side effects from steroids are many and any time an alternative is successful, you’re better off.  Remember, topical steroids are fine, it’s the oral systemic absorption of steroids that contributes to the side effect profile.  

 Due to the long-term side effects associated with high dose corticosteroids and a tendency for relapse after discontinuation, this therapy is not first-line outside of using short bursts and tapers for severe symptoms needing urgent relief (eg, critical dysphagia, stricture, dehydration and acute weight loss.

Topical Corticosteroids

Topical corticosteroid are used in EoE through 1 of 2 routes:

  • “Gulping” the expressed actuations of an inhaled device; or
  • Expressing the contents of a nebulizer respule into a cup, forming a thickened slurry by mixing it with sucralose/maltodextrose (Splenda®), and water.

Use in this manner provides “local” or tailored coating of esophageal tissue, at lower doses (220 μg-1 mg per dose). Faubion and colleagues demonstrated that 880 μg/day of swallowed fluticasone propionate or beclomethasone diproprionate resulted in symptomatic improvement in 4/4 pediatric patients Noel and group at the Cincinnati Children’s Medical Center, noted that non-atopic patients had a better response rate to the topical steroid than the atopic patients.  A randomized, controlled trial by Konikoff and colleagues confirmed similar findings independent of pre-treatment eosinophil numbers. 

Oral viscous budesonide (OVB) is quickly becoming the preferred therapy to fluticasone.

The technique of swallowing a liquid dose may be more effective and efficient than “gulping” a hydrofluroalkane gaseous suspension. Additionally, OVB has comparable efficacy. One study found an 80% decrease in a symptom scoring index and regression of cell counts to less than 7 Eos/HPF; after 3 months of therapy there was decreased fibrosis/remodeling from baseline.

Dosing for fluticasone ranges from 220 to 880 μg per day, and for budesonide, from 0.5 to 2 mg per day; both doses are similar to those used in asthma. With either agent, patients are instructed to not eat or drink for 30 minutes after administration. Complications from topical treatment include oral/esophageal candidiasis.  In a 3-year case series studying recurrence, approximately 90% of adults relapsed at a mean of 8 months post discontinuation of 6 weeks of therapy. Just like asthma, when you stop using the controller medication, symptoms will come back.  No study of optimal dose or duration of therapy has been performed, but most adult providers recommend a 6-week course while pediatric providers suggest a 12-week course.  No long-term safety data exist pertaining to bone or adrenal effects from such small but more readily bioavailable dosing methods used in EoE.

Acid Suppression

Technically, EoE should not be diagnosed until response to PPI therapy has been determined, according to the 2007 and 2011 consensus guidelines. A certain subset of patients will have PPI-responsive esophageal eosinophilia.  Typically, dosing is either 10-40 mg omeprazole or 15-30 mg lansoprazole per dose for 2-3 months. High-dose PPI therapy may distinguish GERD from EoE.

Immunomodulating Therapy

Immunomodulating therapies may offer some promise. The best studied therapy is anti-IL-5. In mice, anti-IL-5 decreases blood and tissue eosinophils, and decreases eotaxin-3 levels. Garret and fellow researchers studied anti-IL-5 in 4 patients with hypereosinophilic syndrome. Symptoms and eosinophilia resolved, and in 1 patient who also had EoE, dysphagia and esophageal eosinophils decreased. Stein and colleagues, in an open-label phase I study of anti-IL-5, noted that blood eosinophilia was reduced but not correlated to decreased levels of IL-5, eotaxin-3, or esophageal eosinophilia.   Similarly, there was no significant difference between groups in symptom improvement. Studies of other agents, such as anti-IgE or anti-TNF (infliximab), failed to demonstrate any symptomatic or esophageal histologic improvement. Presently, anti-IL-3 is under investigation in a phase 1 trial, but no data are available pertaining to its safety or efficacy.

Dilation

Dilation relieves critical esophageal narrowing and related symptoms, but will not alter the underlying pathophysiology. Its benefit is maximized for dysphagia and impaction from ring/stricture or other critical narrowing. Several studies have demonstrated the efficacy of dilation, though it is balanced by risks including perforation, deep mucosal tears, pain, linear renting, and bacteremia. Relief is also likely to be transient, because 75%-50% of patients who receive this therapy have recurrence at 2-20 months and need additional dilation.

Dietary Management

A 6-week trial of 10 patients conducted by Kellyand colleagues in 1995 demonstrated the role of an exclusively elemental diet.  At the conclusion of the study, 8/10 had complete histologic and symptomatic resolution and the other 2 subjects showed drastic improvement, demonstrating an elemental diet as a potential treatment. As with steroid therapy, however, upon discontinuation, all patients relapsed. A larger study of elemental diet therapy in 51 patients was conducted by Markowitz and colleagues.  The researchers noted symptomatic response by 8 days and normalization in biopsy by 1 month in 49 of the patients studied. Liacouras and colleagues followed 389 patients with EoE over 10 years, 160 whom were treated with elemental diet and noted a 97% response rate to the diet and biopsy counts that were comparatively lower than 75 patients on swallowed fluticasone. Though exceptionally effective, elemental therapy is limited in that a patient’s only source of nutrition is a very specific hypoallergenic formula. This may not be appropriate for adolescents or adults. Some cases require placement of gastrostomy tube to assist with feeding.

An alternative approach is a tailored/guided diet that avoids only an individual’s known food sensitizations based on skin prick and/or patch testing. Spergel and colleagues described 120 patients placed on a guided elimination diet based on allergen testing.  After 6-8 weeks, 112 had near complete tissue resolution, though 39 relapsed upon reintroducing eliminated foods. In this cohort, 77% had at least 1 positive prick skin test, and 85% had 1 positive atopy patch test. Prick skin tests were most commonly positive to milk, egg, soy, and peanut. The foods that were most commonly positive to atopy patch test were corn, soy, wheat, and milk. Most patients were sensitized to multiple foods, and dietary nonresponders had more sensitizations than responders. Positive predictive value and negative predictive value for 13 commonly positive foods in EoE were published in a previous post.

Follow-up of patients with EoE should be frequent, at least 4 times per year, with consideration for repeat endoscopy at those intervals as well. Repeat endoscopy is the only way to monitor disease progress, because symptoms do not always correlate with disease progression. One pediatric study found that an initial cell count of 6 or greater was predictive of a repeat positive biopsy.

 At each follow-up visit, diet should be reviewed, diet/medication compliance assessed, and consideration given for additional food testing if symptoms or histology are not improving. As noted previously, there are no studies that have evaluated adequate or optimal duration of treatment for either dietary avoidance or topical steroid duration. Very little formal guidance is available to determine key long term predictors of disease resolution, the optimal interval for repeat biopsy, and the effect of these factors on the development of long term sequelae.

Complications from EoE include:

  • Strictures,
  • Schatzki ring
  • Esophageal trachealization and stretching,
  • Esophageal furrowing and narrowing, microabscesses, webbing,
  • Food impaction, persistent/progressive dysphagia, and lamina propria fibrosis.

Esophageal remodeling in EoE occurs as a result of subepithelial fibrosis and is reported in 15%-40% of affected adults. Predictors that influence the likelihood of developing fibrosis are presently unknown. To date, there is no identified association with progression to malignancy directly from the presence of EoE. Some have observed a potential link between celiac disease and EoE, which may share some common gene upregulations with EoE, but this association is not well understood.

The natural history of food allergy/sensitization within EoE has not been well-described. Lastly, while preliminary work and observation indicates that quality of life can be affected significantly, little formal study of EoE quality of life exists. This particular area of research is very important to continue to define, as the quality of life issues that affected families face are distinct from those of the general food allergy community.

From the Journal of Allergy & Clinical Immunology (In Practice)

 Informational video on eosinophilic conditions

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The Teen Who Can’t Swallow–What is it?

What is the most likely diagnosis?  How did you do compared to your colleagues?

       Your Colleagues Responded:
  GERD    28%
  Eosinophilic esophagitis Correct Answer  67%
  Celiac disease    4%
  Irritable bowel syndrome    1%
 

Eosinophilic Esophagitis: Definition, Epidemiology, and Pathophysiology

Clinical Definition–summary only.

  • Eosinophilic esophagitis (EoE) is chronic, inflammatory esophageal clinico-pathological condition. The diagnosis is made following a biopsy confirming ≥ 15 eosinophils(eos)/high-powered field (hpf), at a minimum of at least 2 esophageal levels (eg, distal and proximal) because the process does not uniformly affect one particular area.
  • Clinical symptoms indicative of esophageal dysfunction, such as dysphagia, odynophagia, and vomiting are present. Additionally, patients generally also note reflux often presenting as chest pain and regurgitation. These symptoms are not diagnostic in the absence of a positive biopsy.

    Eosinophilic esophagitis--both endoscopy & biopsy illustrated
  • Gross features found on esophagogastroduodenoscopy (EGD) may include narrowing, ulcers, or furrowing. Additional histologic features may be seen, such as microabscess formation or fibrosis.
  • However, no histologic or gross finding is diagnostic of EoE beyond peak cell count.

Epidemiology

The earliest literature reports of EoE date to the late 1970s, as case reports of GERD patients unresponsive to H2-receptor antagonists who were found to have numerous eosinophils on esophageal biopsies. Recent evidence suggests that EoE has likely been present for decades, but was poorly recognized. When I was a resident & fellow in the early 90’s we diagnosed many children with “functional abdominal pain”.  Wonder how many of those cases were EoE!

Studies in the mid-1990s demonstrated the role that diet and steroids (both systemic and topical) could play in the disease treatment, which provided evidence that allergy had a relevant role in the pathogenesis and fit the observations that many of these patients were atopic (this means allergic!) Some studies have noted that less treatment-responsive patients tend to have either a personal or family history of atopy. However, up to 25% of all known cases are not associated with atopy.

EoE appears to disproportionally affect non-Hispanic, white, atopic males.  The male-to-female ratio is 3:1, and EoE tends to congregate within families, although no true hereditary link has been established. EoE has been reported on every continent to date except Africa, and across all age ranges, although the typical age of onset is the third or fourth decade of life.

Presenting symptoms vary drastically across the ages, and are summarized in the Table.

Table. Presentation of Eosinophilic Esophagitis: Children and Adults

Children: Appear SICK Adults: Appear WELL!
Failure to thrive (5%-19%) Dysphagia (29%-100%)
Vomiting (5%-38%) Food impaction (25%-100%)
Abdominal pain (5%-68%) GERD (7%-100%)
Diarrhea (1%-24%) Chest pain (1-58%)
GERD (5%-82%) Mild eosinophilia (5%-50%)
Chest pain (17%-20%) Delay in diagnosis!
Dysphagia (16%-100%)  
Food impaction (10%-50%)  

With both age groups, a history of eating slowly, taking small bites, excessive drinking after each bite, and avoidance of textured foods is common and represents compensatory mechanisms.

Pathophysiology

EoE is an allergic disease, but it’s not that simple.  In affected esophageal tissue there is upregulation of interleukin (IL)-4, IL-5, and IL-13 expression.  However, both immune globulin E(IgE) and non-IgE (cellular-mediated) mechanisms contribute, as is seen in atopic dermatitis.

This means that sometimes skin testing is helpful and sometimes it is not.  Foods to eliminate with negative skin tests comes down to trial and error.  IL-5 is the main cytokine responsible for eosinophil maturation, bone marrow development, esophageal remodeling, and signals for eotaxin-3, the most crucial eosinophil chemotaxis factor.  IL-5 deficient mice cannot develop EoE, and intratracheal IL-13 induces dose-dependent EoE. In mice, anti-IL-13 blocked development of EoE. IL-13 induces eotaxin-3 production, and may be an independent factor inducing tissue remodeling.  IL-13 is central to an emerging hypothesis of epidermal barrier dysfunction as a mediator of EoE and directly downregulates gene transcription of filaggrin and involrucin.   

Is there a genetic basis for EoE?  Eotaxin-3 SNP’s are present in 14% of cases, and researchers have identified an “EoE Transcriptome” — a unique set of approximately 1% of genes that are overexpressed in EoE. More recently, a genome wide association study identified a disease susceptibility locus at 5q22, and a polymorphism in TSLP (thymic stromal lymphoprotein).  So in short, yes, genetics play a role, but more research is needed.

Ok, enough of the basic science stuff.  Tomorrow I’ll discuss how to evaluate a patient you suspect has EoE.  And how do you spell that again?

After Thanksgiving Hangover!

Treating Acid Reflux Disease With Diet and Lifestyle Changes

 Need I say more?

Recipe for heartburn!

Do you often experience the pain of heartburn or other symptoms of acid reflux disease? Most patients despise yet another medication to treat reflux.  You might take comfort in knowing that making diet changes as well as other lifestyle changes may be all you need to do. Here’s how. (the above links to WebMD can be trusted)

What Kind of Diet Changes Can Help Acid Reflux?

One thing you can do to reduce your risk for heartburn and acid reflux disease is to eat low-fat, high-protein meals. Also, eat smaller meals more frequently; eat until you’re no longer hungry–avoid eating until you feel full.  You will always eat less if you eat slower; your mother was correct! 

Mother is usually right!

It may also help to avoid certain beverages and foods.

Avoid beverages that seem to trigger heartburn or make it worse, such as:

  • Coffee or tea (both regular and decaffeinated)
  • Other beverages that contain caffeine
  • Carbonated beverages
  • Alcohol

Avoid foods that seem to trigger your heartburn or make it worse, such as:

  • Citrus fruits, such as oranges and lemons
  • Tomatoes and products that contain tomatoes, such as tomato sauce and salsa
  • Chocolate
  • Mint or peppermint
  • Fatty or spicy foods, such as chili or curry
  • Onions and garlic

What Other Lifestyle Changes Can Treat Acid Reflux?

In addition to acid reflux diet changes, see which of the following lifestyle changes you can make.

  • Quit smoking . Smoking may increase your risk for heartburn and acid reflux disease in many ways. For example, it may increase the amount of acid secreted by your stomach and interfere with the function of muscles that help keep acid down.
  • Reduce reflux while sleeping.These steps will help reduce reflux when you sleep:
    • Put blocks under the head of your bed to raise it at least 4 to 6 inches. This helps keep your stomach’s contents down. However, it doesn’t work to simply use lots of extra pillows because this position may increase pressure on your abdomen.
    • Stop eating at least two or three hours before lying down.
    • Try sleeping in a chair for daytime naps.
  • Lessen the pressure.Often, extra pressure around your abdomen increases acid reflux. Try these steps:
    • Don’t wear tight clothes or tight belts.
    • If you’re overweight or obese, take steps to lose weight with exercise and diet changes.  Here again, WebMD has some great tips to get started.

Can Medication Help Heartburn?

Over-the-counter medications can help neutralize stomach acid. Be careful at this point.  Antacids and ranitidine (called Zantac™) are very weak–I would recommend starting with Prilosec™ or omeprazole. Use 20mg morning and evening until symptoms are well-controlled.  Antacids may give quick, short-term relief for many people, but it doesn’t take care of the “root” of the problem, that is oversecretion of acid from the stomach.  If you find you need to keep taking OTC meds  for more than two weeks, see your doctor or other health care provider.

Also, ask your doctor whether any medication could be triggering your heartburn or other symptoms of acid reflux disease. These are examples of medications that may trigger acid reflux:

  • Aspirin or NSAIDs, such as Motrin
  • Some muscle relaxants
  • Certain blood pressure drugs

Want more information on GERD or heartburn?  Look no further–AAAAI!