HEARTBURN AND CHOKING – IS IT ALL DUE TO REFLUX?

Peggy MarconHospital for Sick ChildrenNorthern Ontario Pediatric Conference

Declaration

I have nothing to declare.

Physiology Lesson

TLESRGastric Emptying

Meal Size and Content

Definitions

Regurgitation: sudden effortless exteriorisation of a variable quantity of liquid derived from the stomach or esophagus into the mouth or the pharynx

Vomiting: generally preceded by nausea and associated with abdominal muscle contractions, resulting in involuntary forceful emission of gastric contents into the mouth

Rumination: The voluntary return of food to the oropharynx. The food is then either re-swallowed or spit out.

Case 1

A very concerned mother brings her 4-week-old boy to your office

Uncomplicated pregnancy and birth weight 4,150 g

Breast feeding

Regurgitates a lot

No other health issues

Especially no eczema / constipation / diarrhea

It gets worse before it gets better!

Treatment for Simple GERD in Infancy

Review feeding practice

No smoking

Reassurance

Position

Nutritional Therapy

Breast feeding / Breast milk Formula change – protein intolerance syndrome

Thicken formula

THERE IS A HUGE OVERLAP WITH “CLASSIC’ INFANT GERD AND PROTEIN INTOLERANCE!

**Thickening agents / Commercial thickened formula should not** be used indiscriminately in healthy thriving infants.

*Orenstein Pediatr 1987;110:181-186 *Vandenplas Clin Pediatr 1987;26:66-68 *Wenzl Pediatrics 2003;111:e355-59 *Aggett JPGN 2002;34:496-498

Clinical Presentation:Warning signs in Infants

Irritability**

Feeding Resistance**

Failure to Thrive

Hemetemesis

Anemia**

Posturing (Sandifer’sSyndrome).

**Protein Intolerance / Allergy?

Recurrent pneumonia

Wheezing and asthma

Apnea

Stridor and recurrent croup

Treatment for Complicated GERD in Infancy

Acid Blockade H2 Blockers

PPI

Prokinetics Metaclopramide: now contraindicated in infants

Domperidone: suggest baseline and dose increases ECG

Nutritional Rehabilitation

Tube supplementation

Surgery

Clinical Presentation of GERD

In infants and children with oromotorproblems simple regurgitation

can be life threatening problem!

COULD IT BE THE FOOD THAT IS THE PROBLEM?

GER:

• Regurgitation > vomiting

• Irritability shortly after feed

• Arching

• Rumination**

• Feeding difficulties**

• Bowel movements: usually normal

CMPA

• Vomiting > regurgitation• Irritability: 30 m to 2 h • Rumination**• Feeding difficulties**• Gas ++• No problem during feedings• Diarrhea (mucousy stools) or

severe constipation• Rectal bleeding• Atopic dermatitis• Eosinophilia, thrombocytosis,

mild hypoalbuminemia

“Allergic Disease” in the Breast fed baby

Unclear if there is a role for restricted maternal diet during pregnancy.

For infants with atopy, colitis or possibly GERD and severe constipation you may want to restrict mother’s diet.

Breast Milk Fortifers are CM based.

Feeding behavior

Infants with simple GERD* / n=63 / control = 93 4% of infants had resistance to oral feeding severe enough to

require a tube.

Children’s Eating Behavior Inventory

Feeding and mealtime problems at 1 year f/u.

8% case vs. 0% control: ‘my child takes more than an hour to eat.”

14% case parents vs. 4% control parents: “I get upset when I think of our meals.”

Nelson Pediatrics 1998;102:E67. * Some of these may have had prointolerance

After Infancy

2nd case

A 12 year old boy comes to see you because he has been experiencing stomach aches and on questioning waterbrash. Otherwise he is well – what advice to you give?

GERD: at increased risk

Prematurity

Neurologic disease

Hypotonia / Myopathies

Chronic Lung Disease ?Asthma

Cystic Fibrosis

Congenital Esophageal Anomalies / Foregut anomalies

Increased Abdominal pressure

Chromosomal Anomalies

Syndromes

Collagen Vascular Disease

Drugs

Obesity

Hiatus Hernia (especially congenital)

Simple heartburn

Try conservative measures

Review medication and supplement use

No second hand smoke

Trial of PPI or H2 Blocker for 8 weeks

Adolescence –

NO smoking including marijuana and E Cigs

Check how much alcohol use

If they had change infant formula to a non dairy based formula you might stop dairy products.

Rumination

Effortless “regurgitation” that is

either swallowed back or spit out

20 or 30 times a day

Often bothers the parents more than the child unless happening at school

May be “learned” from an organic problem that may still be on going or has resolved.

Always needs behavioral intervention

RISK: ASD, Neurologic impairment,

TIC, anxiety and depression

Prevalence of GERD Symptoms in Children

Nelson SP et al. Arch Pediatr Adolesc Med 2000;154:150-54

1.8%

7.2%

2.3%

5.2%5.0%

8.2%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

Heartburn Epigastric pain Regurgitation

% o

f ch

ild

ren

Reported by the parents (children age 3-9 years) (n=566)

Reported by children (age 10-17 years)

(n=615)

Erosive esophagitis

In Children with GERD symptoms without co morbidities for whom an endoscopy is indicated: 34.6%

In Neurologically impaired children: 30-70%

In GER Infants and children without c morbidities :: < 5%

Respiratory manifestations: 20%

In children with GERD symptoms :

Asthma 13.2%;

Pneumonia 6.3%

ENT manifestations: 6.9%

In children with GERD symptoms :

Sinusitis 4.2%;

Laryngitis 0.7%; otitis media 2%

Epidemiology of Reflux Complications in Children

El-Serag HB et al. Am J Gastroenterol 2002;97:1635-39

El-Serag HB et al. Gastroenterology 2001;121:1294-99.

Evaluation for GERD:

Upper gastrointestinal barium study (UGI) To look for anatomical problems

+ SB series if indicated

+ “marshmallow” for solid food dysphagia

Videofluoroscopic Feeding Study If have concerns re oromotor coordination

Nuclear Medicine Studies

24 hour Intraesophageal pH study “Gold” standard

Maybe Impedance

Upper gastrointestinal endoscopy A “must” for solid food dysphagia

Management of GERD

Lifestyle

Nutrition / Diet changes

Medication

Surgery

Indications for Treatment in Children

Mild esophagitis:• 8 weeks PPI full dose treatment.

• PPIs on demand or Step-down strategy (H2RA on-demand)

• If relapse or PPI dependent: surgery?

Severe esophagitis, stricture, Barrett, neurological impairment:• 8 weeks PPI full dose treatment.

• Maintenance therapy w/ PPI or

Asthma + GER:• PPI full dose treatment for at least 6 months

• Evaluation

• If improvement : Maintenance therapy? Surgery?

Rudolph CD et al. JPGN 2001;32:S1-31

Khoshoo V et al. Chest 2003;123:1008-13.

Treatment

PPI Rules

1 to 3 mg/kg

Up to Adult dosing

Rate of metabolism is genetic: slow, middle and fast.

Faster and better response than H2

? H2 better in infant EoE

Omeprazole dissolved for gtubes

Prevacid FasTAb Not covered ODB

Ranitidine

5 - 10 mg/kg/day tid

(300mg divided bid)

Tachyphylaxis

Recent “suggested” issues with PPIs ↑Community acquired pneumonia

↑Upper respiratory Infection

↑C. difficle infection

↑ Risk of fractures

Decreased Mg+

Pharmacotherapy: Promotility

Prokinetic *Cisapride

0.8 mg/kg/day qid (10-20mg qid) ECG

**Domperidone 1.2-2.4 mg/kg/day (30mg/day) ECG

Metoclopramide No use under 1 year e Smaller dosing: 0.5 mg/kg/day)

Treatment for GERD: On the Net!

Quote “Apple Cedar Vinegar is a

Natural remedy for acid reflux”

Even Dr. Oz says – but

No good studies published – but there is a chewing gum with this that might help!

It may be the licorice in the gum!

Melatonin may help

Step Down Approach

Shown in adults to be clinically and economically better

PPI

H2 Blocker

Outcome?

Various studies suggest GERD may go away and other say stay long-term in children and adolescents.

Risk of developing Esophageal Cancer in someone with Barrett’s esophagus is 1%.

Current “rewriting” what to do with adults Some groups are at increased risk of

Barrett’s and Esophageal Cancer: TEF / Some Syndromes / Erosive esophagitis

Case 2

He returns after two months still complaining of heartburn and now occasionally has difficulty getting some foods down? BBQ chicken stuck last weekend.

What advice to you give now?1. Increase the dose of the PPI

2. Add antacids

3. Referral for further investigation

4. Relaxation therapy

EoE Explosion Incidence of EoE varied from 0.7 to 10/100,000 per

person-year

Prevalence ranged from 0.2 to 43/100,000.

Based on review of 25 studies J Pediatr Gastroenterol Nutr. 2013 Jul;57(1):72-80. Incidence and prevalence of eosinophilic esophagitis in children

Male

Females

This is from a study looking at the rise inboth EoE and Celiac Disease

EoE

EoE is a clinicopathologic disorder diagnosed by clinicians taking into consideration both clinical and pathologic information without either of these parameters interpreted in isolation and defined by the following criteria:

Esophageal symptoms

≥ 15 eosinophils/hpf

Isolated to esophagus, persists after PPI trial

Secondary causes excluded

(responds to dietary or steroid therapy) Am J Gastroenterology 2013; 108:679-692

Epidemiology

Infancy thru adolescence and now

well reported in adulthood.

Male > Female.

2/3 history of atopy

Reported in families (father / son)

PPI responsive and non responsive

Remedios Gastrointestinal Endoscopy 2006;63:3-12.

Classic EoE

Barium study most often NORMAL

Tram tracking and trachealization

Diagnosing it: defined by # of eosinophils in the biopsy

Oren

stein GER Eosinophilic esophagitisNormal esophagus

Other Investgations

May or may not have a peripheral eosinophilia(50%).

Hemoglobin and serum albumin are often normal. IgE may or may not be elevated. RAST testing has generally NOT been helpful. Patch testing may be helpful. Barium swallow often read as normal.

Other causes of esophageal eosinophilia EGE

PPI-responsive esophageal eosinophilia*

Celiac disease

Crohn’s disease

Infection (be careful – may predispose to infection)

Hypereosinophilic syndrome

Achalasia

Drug hypersensitivity

Vasculitis

Pemphigus

Connective tissue diseases

Graft vs. host disease

EE treatment

Local steroids

Systemic Steroids

Diet (elemental vs. elimination)

Mast cell stabilizers

Anti-IL 5 antibodies

Steroids and EE

Topical corticosteroids

Fluticasone swallowed in divided doses:

Children: 440 – 880ug/d x 6-8weeks

Adolescents/adult: 880 – 1760ug/d x 6-8 weeks No spacer

No food or drink for at least 30 minutes after ingesting the dose

x 4 weeks then taper over 6 weeks

Budesonide children: 1-2mg daily x 3-4 months

adults*: 2-12mg daily x 2-6 weeks

Mix with Splenda®

Easier said then done!

Changing His Diet

Diet Therapy

Elemental (formula based) Very effective: 86 to 95% remission Hugh effect of QofL if used longterm Aim to then go thru food reintroduction

Skin prick and history guided 78% had significant clinical and histological remission. Soy, wheat, chicken, and beef most frequently identified

6 Food Elimination Cow’s milk protein, soy, wheat, egg, peanut/tree nut, and fish/shellfish were the only

foods excluded 74% of children and adults had significant clinical and histological

4 Food Elimination Dairy products, wheat, egg, and legumes 54% remission with additional 31% when changed to 6 food

In all cases Dairy is a big issue

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And where do adolescents fit?

Food choices?Best plan is a dietitian

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One food elimination diet?

Prospective, comparative effectiveness trial of cow's milk elimination and swallowed fluticasone for pediatric eosinophilicesophagitis.

Dis Esophagus. 2015 Feb 26. [Epub ahead of print] Eo

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No Milk Topical Steroids

Outcome

▼ eos 64% 80%

Symptomscores

Improved Improved Equal

QofL Improved Improved Equal

Maintenance Therapy

All of these patients want to know

what to do so they feel well

and can eat “normally”.

Do I do Dietary Therapy?

Do I do Drug Therapy?

Role of Dilation?

Or some combination of the above?

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Easier way to follow food reintroduction? Esophageal String Test

Furuta GT et al. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut 2013;62:1395–1405.

Cytosponge Katzka DA, Geno DM, Ravi A, et al. Accuracy, safety, and tolerability of tissue

collection by cytosponge vs endoscocpy for evaluation of eosinophilic esophagitis. Clin Gastroenterol Hepatol 2015 Jan;13(1):77-83

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Allergist?

All the reviews recommend seeing an Allergist to look for IgE mediated allergies that may be contributing to issues.

Remember the actual mechanism(s) of disease are unknown and foods not picked up on skin prick testing can be significant issues

Most places find Patch testing not helpful

RAST testing has been unhelpful

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Etiology

J Gastrointestin Liver Dis. 2013 Jun;22(2):205-8. De-novo onset of eosinophilic

esophagitis after large volume allergen exposures.

Lawn mower Moldy house Renovation

My patient – cleaning the grain silo out with his father!

Other Pharmacological Treatments Mast cell stabilizers

Case series suggest that liquid preparation of Cromolyn offers benefits

Leukotrienes inhibitors (Montelukast) One study showed clinical improvement but no impact on

esophageal eosinophilia.

Ketotifen Useful for Eosinophilic gastroenteritis and colitis

Not clear if useful for “classic” EE

Role of PPIs not clear. Does it worsen allergic issues?

Maintenance Therapy in EoE

Disease waxes and wanes

Best long term options not clear

Choices are

Pharmacotherapy

Diet Therapy

Combination of above

Role of dilation in combination with PPI?

Long term compliance is also an issue!

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GERD Guidelines

Guidelines for the Evaluation and

Treatment of Gastroesophageal Reflux

in Infants and Children

Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) J Pediatr Gastroenterol Nutr 2009;49:498-547

www.naspghan.org

http://www.gikids.org/

Downloadable handouts for patients and parents at this site including coloring books!

Guidelines EoE

Am J Gastroenterol 2013; 108:679–692

ESPGHAN: Journal of Pediatric Gastroenterology & Nutrition: January 2014 - Volume 58 - Issue 1 -p 107–118

NASPGHAN in Gastroenterology 2007;133:1342–1363