Eosinophillic oesophagitis Hendricks

Eosinophillic

oesophagitis L. Hendricks

Supervisors:

Dr L. Goddard

Dr M. Levin

Dr P. Walabh

Eosinophilic Oesophagitis Hendricks

April 2012

Case TA • 1 yr male presented to RXH in 1998

- recurrent PAO since 3/12 age

- diagnosed as GORD after Ba swallow and was started

on Gaviscon and Cisapride

- was lost to follow up

- presented again 9 yrs later complaining of heartburn

and epigastric pain

• Also atopic history: asthma, urticaria and food allergies

• Atopic family history


April 2012

Case TA - Ba swallow repeated: normal anatomy and reflux to the

level of the hypopharynx started on omeprazole

- seen at GIT clinic and scoped: H. pylori infection and

gastritis multiple courses of omeprazole and

antibiotics with no improvement

• FBC and diff: normal


April 2012

Case TA • Scopes – March 2009: H. pylori infection and reflux (3

specimens taken)

- Feb 2010: eosinophillic oesophagitis 60/hpf (

4 specimens taken)

• SPT , APT and RAST – potato, rice, carrot, green beans,

chicken, beef, peanut and cow’s milk

• July 2010 biopsy repeated: EoE resolved (5 specimens

taken)

• Elimination diet : not very compliant

• Despite treatment, still has recurrent symptoms


April 2012

Definition • chronic, immune/antigen-mediated oesophageal disease

• characterized clinically by symptoms related to

oesophageal dysfunction and histologically by

eosinophil-predominant inflammation of oesophageal

mucosa

• Diagnosis is established by the presence of eosinophilic

infiltration of the oesophageal mucosa (more than 15

eosinophils/ high-power field (HPF))

• No infiltration in other parts of the GI tract


April 2012

History • First described in 1978

• increasing prevalence of the disease, particularly since

1995

• ? due to a truly increasing incidence or reflection of

increased recognition by pathologists and clinicians


April 2012

Aetiology • Unclear

• Allergic (allergies to food or aeroallergens) and

immunologic mechanisms

• ?genetic susceptibility - A particular single nucleotide

polymorphism in the eotaxin-3 gene is present in some

individuals with eosinophilic oesophagitis


April 2012


April 2012

Pathophysiology • Oesophagus is normally devoid of eosinophils

• EoE thought to be mediated by IL-5 (cytokine produced by TH2 lymphocytes) and eotaxin (an eosinophil chemotactic factor)

• In sensitized individuals, allergen exposure leads to IgE mediated mast cell degranulation, which leads to the production of chemokines, histamine, and eosinophilic chemo attractants

• These then induce eosinophil migration and degranulation, releasing products such as major basic protein (MBP), eosinophil cationic protein, and eosinophil-derived neurotoxin


April 2012

Pathophysiology • These products cause tissue damage, oedema, chronic

inflammation which, if prolonged, can lead to fibrosis

• The effect of eosinophil products such as MBP on

smooth muscle has also been described, with muscarinic

M2 receptors mediating smooth muscle contraction. This

may explain the ability of eosinophilic infiltration of the

oesophagus to lead to dysphagia and FI, analogous to

bronchoconstriction in asthma


April 2012

Clinical manifestation • Male> Female

• Caucasian

• age at which the symptoms develop varies considerably

• Chest pain, abdominal pain, diarrhoea, and weight loss

• poor feeding, vomiting, regurgitation, and failure to thrive

• Less common symptoms include hematemesis, and

oesophageal dysmotility


April 2012

Adults

• Dysphagia

• Food impaction

• Heartburn/acid

reflux not

responsive to

medical

treatment

• Chest pain

Infants and

toddlers

• Feeding aversion

• Failure to thrive

• GORD symptoms

not responsive to

medical treatment

Young children

and adolescents

• Vomiting,

regurgitation

• Abdominal pain

• Chest pain

• Dysphagia

• Food impaction


April 2012

Dysphagia • Dysphagia: mild, intermittent, related to feeds

• Patients compensate by eating slowly, drinking after

each bite, taking small bites, chewing excessively, or

avoiding specific food consistencies that are problematic

such as meat or bread


April 2012

Vomiting • an overt and immediate allergic response to a recently

ingested food vs. chronic, episodic, unpredictable

vomiting

• Food allergies may also be associated with other

manifestations e.g.. hives, diarrhoea, pain, or even

anaphylaxis

• NB: Retching to remove a piece of food that is stuck may

be called ‘‘vomiting’’ by some patients!!


April 2012

Clinical • Eczema, chronic nasal congestion, recurrent

bronchospasm, and repeated URTI become apparent in

the first 2 years of life

• although the GIT symptoms respond to dietary

restriction, the asthma is generally an independent

phenomenon requiring standard therapy and does not

resolve as a result of diet change alone

• Some of these children have been extraordinarily

sensitive to food and exhibit recurrent eosinophilic

esophagitis with virtually any food added to the diet


April 2012

Associated conditions • many children with eosinophilic esophagitis may have

other medical conditions with symptoms that may

overlap, contribute to, or serve to confuse the issue at

presentation

• coexistence of other allergic diseases - allergic rhinitis,

asthma, skin or food allergies, eczema

• Often family history of atopy


April 2012

Associated conditons • Oesophageal involvement in patients with eosinophilic

gastroenteritis (Diarrhoea, anaemia, hypoalbuminemia, FTT,

and GIT bleeding are NOT typical features of isolated

eosinophilic esophagitis)

• underlying CNS or neurodevelopmental - intractable seizures,

CP, Chiari malformation, PDD, sensory integration disorder,

migraine (very uncommon)

• Hypersensitivity to antiepileptic drugs has been implicated in

the development of eosinophilic esophagitis (rare)

• CHARGE syndrome,VATER syndrome, Pierre-Robin

syndrome, Klinefelter’s syndrome, Moebius syndrome, and

Pfeiffer syndrome(rare)


April 2012

Diff Dx • GORD (eosinophilic esophagitis is seldom diagnosed in

the first 6 months of life when GORD is common)

• Infections e.g. acute GE, herpes, candida

• Food protein intolerance (e.g. milk)

• Other organic causes of vomiting and FTT (metabolic disease, etc)

• Eosinophilic gastroenteritis with oesophageal involvement

• Psychiatric/behavioural disorders

• Drug hypersensitvity response, ct disease, hypereosinophilic syndrome(rare)


April 2012

Special investigations 1.) Nutritional assessment

• Full nutritional assessment

• Exclude TB and HIV (as causes of malnutrition)

2.) Exclude reflux

• Ambulatory pH studies – normal

• Manometry - Most patients have normal results

- Most common abnormal findings being nonspecific peristaltic abnormalities and incomplete LES relaxation


April 2012

Special investigations 3.) Diagnostic tests

• FBC with diff - peripheral eosinophilia (>300-350 per mm3)

• Barium study - proximal and distal oesophageal strictures, diffuse narrowing of the oesophagus

4.) Allergy testing

• skin prick testing - 2/3 of patients have positive reactions to one or more foods; common foods include peanuts, eggs, soy, cow milk, and wheat

• skin patch testing

• combination of testing had a negative predictive value of 88% to 100% for all foods except milk, which was low, while the positive predictive value was greater than 74% for the most common foods causing EE


April 2012

Special investigation • APT is thought to provide evidence for a T-cell–mediated

reaction.

• APT is performed by using the allergen in an occlusion

aluminum Finn Chamber for 48 hours on a patients back

• The chamber then is removed, and the reaction is

measured for induration and papules 24 hours later (ie,

72 hours after placement)

• A true-positive reaction is seen not when the patch is

removed at 48 hours, but 24 hours later.


April 2012

Special investigations • The method for SPT involves placing the allergen on the

forearm or back, pricking the skin with a device, and

measuring the wheal and flare reaction.

• If the wheal diameter is greater than 3 mm, the test is

considered positive

• Specific IgE testing, skin prick testing, and atopy patch

testing have been reported to be positive in variable

(32%–80%) proportions of adults and children with EE


April 2012


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Endoscopy • Proportion of patients may have normal-appearing

mucosa

• Features suggestive of EoE: the presence of rings, narrowing, longitudinal furrows, raised white specks, which may represent eosinophilic microabscesses whitish exudates; and ‘‘crepe paper’’ mucosa, which refers to a friable mucosa that tears by the mere passage of the endoscope

• Strictures can be located in the proximal, middle, or lower third of the oesophagus

• Biopsy should always be performed even if scope looks normal!


April 2012


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April 2012

Oesophageal biopsy • multiple biopsy specimens should be obtained from different

oesophageal locations along the length of the oesophagus

• Diagnostic sensitivity of 100% if 5 biopsies taken

• Peak count of greater than or equal to 15 eosinophils/HPF in at least one HPF is diagnostic

• NB: peak eosinophil count must be measured (useful to measure response to treatment)

• eosinophilic microabscesses

• superficial layering of the eosinophilic infiltrate in the upper half of the oesophageal mucosa

• basal zone hyperplasia

• epithelial oedema


April 2012

Complications • Stricture

• Food Impactions

• Rupture:

–Spontaneous: Boerhaave’s syndrome

–Iatrogenic:

•More common with rigid endoscopy

•Can lead to pneumomediastinum and

pneumoperitoneum


April 2012

Dietary intervention • Success rates of 77% to 98% in inducing clinical and

histologic remission by elimination of all potential food

antigens

• 3 options:

1. elemental amino acid formula (4-6 week duration, not

recommended)

2. Empiric elimination diet: removing foods most likely to be

associated with eosinophilia (such as dairy, eggs, wheat, soy,

peanuts, and fish), for 2-3 months duration

3. Target elimination diet: eliminating specific foods indicated by

allergy testing by skin prick or patch testing (for 2-3 months

duration)


April 2012

Dietary intervention • Don’t forget about supplementation!! (micronutrients,

vitamins, minerals : Ca, Fe, Zinc, Vit D and E)

• Deworm all patients

• Commonly, esophagitis returns without overt symptoms

during attempts at reintroducing food to the diet or upon

withdrawal of steroid therapy

• debate as to whether the symptom(s) or the histology

should be treated


April 2012

Dietary intervention Basic nutritional requirements:

• Carbohydrate intake should provide 45% to 55% of total

calories

• protein should comprise 15% to 20% of the diet,

• fat provides the remaining 30% to 35% of total calories


April 2012

Reintroduction of feeds • After symptoms resolve and biopsy is clear

• Reintroduce one food at a time

• repeat endoscopy 4 to 6 weeks after the introduction of

four or five new foods

• Food reintroduction begins with the least allergic foods

and progresses slowly to the most allergic foods

• If a patient develops symptoms, the eliminate the last

food reintroduced and wait until symptoms return to

baseline before continuing


April 2012

Treatment 1.) Corticosteriods

• Systemic steroids are able to induce symptomatic and

histologic remission

• However, significant systemic toxicity with prolonged use

• Alternatively, swallowed topical corticosteroids

(fluticasone propionate or beclomethasone) induces

symptomatic remission

• Relapse of symptoms in a large percentage of patients

• most common adverse effects are oral candidiasis


April 2012

• Fluticasone (puffed and swallowed through a metered-

dose inhaler)

Adults: 440-880 mg twice daily

Children: 88-440 mg twice to 4 times daily (to a

maximal adult dose)

• Budesonide (as a viscous suspension)

Children (<10 y): 1 mg daily

Older children and adults: 2 mg daily

• NPM for 30 min after steroids taken


April 2012

Treatment 2.) Leucotrienne antagonist

• Shown to have some symptomatic relief

• Histologic improvement not observed

• not recommended


April 2012

Treatment 3.) Acid suppression

• eosinophilic esophagitis is distinguished from reflux by the failure to respond to aggressive antireflux therapy

• They often occur concurrently though

• All children with EoE should be treated with a PPI prior to biopsy (for 6-8 weeks)

4.) Biological agents (Mepolizumab anti-IL-5 monoclonal antibody)

• IL-5 plays a crucial role in the production, recruitment, and activation of eosinophils in the oesophagus

• Preclinical studies have found that monoclonal antibodies to IL-5 or IL-5 gene deletion block the induction of EE in mice

• It has also been shown that monthly administration of IV monoclonal antibody to IL-5 in a patient who had hypereosinophilic syndrome along with oesophageal eosinophilia resulted in a resolution of oesophageal and systemic eosinophilia within 3 months, which raises the possibility of similar agents being tried in patients who have EE who are resistant to conventional medications


April 2012

Treatment 4.) Endoscopic treatment

• Oesophageal dilations – high risk of perforation, pain

and mucosal lacerations

• in patients who are refractory to medical management

with underlying strictures


April 2012


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April 2012

Long Term Outcomes • natural history and clinical course of EoE is thought to be

characterized by recurrent symptoms but remains poorly

defined

- recurrent solid food dysphagia occurring at least once a

week

- The clinical course of patients who had EoE was

characterized by recurrent symptoms in 40% of patients

responding to medical or endoscopic treatment, with EE

also appearing to be a recurrent relapsing disease in a

substantial proportion of patients


April 2012

Long Term Outcomes • Straumann and colleagues :followed 30 adults who had EE (>24

eosinophils/HPF) with periodic dilations alone during a mean of 7.2 years.

• Quality of life was affected severely in only 1 patient and in a minor manner in 15.

• Nutritional status was not compromised in any patient.

• Of the 30 patients: 11 were treated with endoscopic dilation; of these, 4 had repeated dilations and 7 required only a single dilation. The remaining 19 patients were monitored only.

• Patients who had peripheral blood eosinophilia and severe endoscopic abnormalities were more likely to relapse than those who did not.

• Although fibrosis of the lamina propria was noted in later biopsies, no progression to deeper layers or to other parts of the GIT was

• observed.

• No patient developed oesophageal carcinoma or hypereosinophilic syndrome. Hence, EE does not appear to influence life expectancy


April 2012

Family education • Support families

• Regular follow up

• Multidisciplinary team


April 2012

Summary • EoE is characterized by symptoms related to esophageal

dysfunction and eosinophil-predominant inflammation

• 15 eosinophils/hpf (peak value) is considered a minimum threshold

• The disease is isolated to the esophagus

• There is an important link between atopy and EE

• Removal of the most common foods is effective in approximately 70% of patients who have EE

• The disease should remit with treatments of dietary exclusion, topical corticosteroids,or both

• However, relapse is very common


April 2012

Many issues unresolved • Optimal end points of treatment (eg, symptom relief and

histologic normalcy)

• Frequency of endoscopy in follow-up (Is it needed in

asymptomatic patients?)

• Maintenance treatment (dose and duration)

• Validated measurements of symptoms, endoscopic

findings, histology, and quality of life


April 2012

References • 1. Eosinophilic Esophagitis in Adults

• Ganapathy A. Prasad, MD, MSa, Nicholas J. Talley, MD, PhD, FRACP, FRCP, FACPb

• aDivision of Gastroenterology and Hepatology, Alfred Main, GI Diagnostic Unit, Mayo Clinic College of Medicine

• 2. Eosinophilic Esophagitis in Children: Clinical Manifestations

• Philip E. Putnam, MD, FAAP

• Cincinnati Center for Eosinophilic Disorders, Division of Gastroenterology, Hepatology, and

• Nutrition, Cincinnati Children’s Hospital Medical Center

• 3. Eosinophilic Esophagitis

• Chris A. Liacouras, MD

• 4. Eosinophilic Gastroenteritis

• Seema Khan, MDa,*, Susan R. Orenstein, MDb

• aThomas Jefferson University Medical School, Division of Pediatric Gastroenterology

• and Nutrition, Alfred I. DuPont Hospital for Children

• 5. Food Allergies and Eosinophilic

• Gastrointestinal Illness

• Nirmala Gonsalves, MD

• Division of Gastroenterology, Northwestern University, The Feinberg School of Medicine,

• 6. Eosinophilic oesophagitis

• Mike Levin, Allergy and Asthma Clinic, Red Cross Hospital


April 2012

References 7. Eosionphilic oesophagitis in Cape Town, South Africa

Michael Levin and Cassim Motala

Clinical and Translational Allergy 2011, 1(Suppl 1):P26 doi:10.1186/2045-7022-1-S1-P26

8. Nutritional Management of Eosinophilic Esophagitis

Jonathan M. Spergel, MD, PhD, Michele Shuker, MS, RD, CSP, LDN

9. Long-term outcomes in pediatric-onset esophageal eosinophilia

Charles W. DeBrosse, MD, James P. Franciosi, MD, MS, MSCE, Eileen C. King, PhD,

Bridget K. Buckmeier Butz, MHSA, Allison B. Greenberg, BA, Margaret H. Collins, MD,d J. Pablo

Abonia, MD,Amal Assa’ad, MD, Philip E. Putnam, MD, and Marc E. Rothenberg, MD, PhD

Cincinnati, Ohio

10. Eosinophilic esophagitis: Updated consensus recommendations for children and adults

Clinical reviews in allergy and immunology

ChrisA. Liacouras,MD,GlennT. Furuta


April 2012

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Eosinophillic oesophagitis Hendricks