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APAPARI FOOD ALLERGY CASES - 1

Professor Pakit Vichyanond, MD

Department of Pediatrics

Faculty of Medicine Siriraj Hospital, Mahidol University

THE BIG EIGHT FOODS CAUSING FOOD ALLERGIES

Case #1 – Bloody-mucous stool in a 3 month-old boy

A 3-mo-old boy presented with specks of blood and mucous in the stool for 2 weeks.

The child is on exclusive breast-feeding.

The mother is a highly educated woman and is on a balanced diet.

Physical examination of the boy – a healthy infant with a complete normal examination.

COW MILK HYPERSENSITIVITY

• Is head-to-head with egg

hypersensitivity among FA patients

• Range of symptoms

• Pure IgE mediated – anaphylaxis

• Pure ‘non-IgE’ mediated – proctocolitis,

Food Protein-induced Enterocolitis

(FPIES)

• Mixed type – atopic dermatitis and

other rashes syndrome

All pictures are shown with families’permission

All pictures are shown with families’permission

Accidental Exposure to Cow’s Milk in a Thai Girl 2013 FPIES

(FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME)

• Symptoms – recurrent vomiting, diarrhea, lethargy, pallor dehydration and could lead to hypovolemic shock

• Common age 2 mos – 1 year

• Occur within 1-3 hour of feeding

• Most common cause = cow’s milk

• Other causes – solid foods eg rice, soy , chicken, fish, egg, etc

• Commonly resolved by 3 years of age

Guibas et al. Pediatr Allergy Immunol. 2014 May 23. doi: 10.1111/pai.12237.Katz et al. J Allergy Clin Immunol 2011;127:647-53

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AGE OF OCCURRENCE OF CMA AND FPIES IN ISRAEL

• Incidence of FPIES = 0.34%• Usual amount of milk causing

symptoms = 120 ml• 8/44 went onto develop IgE-

mediated CMA

FPIES

IgE-CMA

Katz et al. J Allergy Clin Immunol 2011;127:647-53

Katz Y et al. J Allergy Clin Immunol 2010;126:77-82

Case#2, A 7-mo-old girl with urticarial after breast feeding

A 7 mo-old-gril with history of atopic dermatitis at 2 mos of age.

Seen by a dermatologist – treated with emollient and steroids cream –responding well to therapy.

Seen by you at 3 mos of age – mild AD was noted. SPT 2 x 2 wheal to egg white, 4 x5/10 x 10 to peanut. Advise to maintain BF and no maternal diet restriction.

At 7 mos of age, at follow up visit, mom showed you pictures of the child with urticaria on 5 occasions (see pictures)

What is the cause of the reactions? And what would you do further?

Egg white = 2/3 of egg weightsEgg yolk = 1/3 of egg weights

1 eggs = 60-70 gm

SPECTRUM OF EGG SENSITIVITY

• Atopic dermatitis

• Food allergy and anaphylaxis

All pictures are shown with families’permission

EGG SENSITIVITY

• Eggs are among the most common food

causing allergy in infants/children

worldwide

• Healthnut study – Melbourne 2012

• 2848 children randomly selected at 1

year of age

• Prevalence of egg sensitivity = 16.5%!!!!

• Positive egg challenge = 8.9%!!!! 0

2

4

6

8

10

12

14

16

18

SPT+ 1mm SPT+ 3 mm Challenge Pos

The Healthnut Study – Children 1 year of age - Melbourne

Egg Milk Peanut Sesame Shrimp

Osborne et al. J Allergy Clin Immunol 2011;127:668-76

FOOD ALLERGY AMONG CHINESE INFANTS

Chen J, Hu Y, Allen KJ, et al. The prevalence of food allergy in infants in Chongqing, China. Pediatr Allergy Immunol, 2011, 22(4): 356-360

497 infants were screened, 80 were challenged. 18 were positivePrevalence = 3.8 (CI 2.5-5.9%) Egg 12, milk 6

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Case #3, A 13-year old boy developed urticarial and collapse after exercise

A 13-yr-old Thai boy presented with difficulty to breath and urticarial after exercise (jogging) since 7 years of age.

There were 8 similar episodes during the last year.

Treatment included ER visits and injections of adrenaline.

The family consulted you for the questions

What causes this condition?

What should they do?

Will he grow out of this problem?

EXERCISE-INDUCED WHEAT-DEPENDENT ANAPHYLAXIS

CHALLENGE PROTOCOLDay Type of challenge Result

1 Exercise Negative

2 Wheat Negative

3 Pizza then exercise Anaphylaxis

Skin prick test:Histamine: 8X6 mmWheat: 10X6 mmPizza: 5X5 mm

REPORT ON WHEAT ANAPHYLAXIS

WHEAT ANAPHYLAXISA GROWING PUBLIC CONCERN

Wheat-induced Anaphylaxis

Amount of Noodleuse in the challenge

Skin reaction towheat extract

Anaphylaxis to wheat in a 4 year old girl

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Prof Hugh SampsonMount Sinai, New York

Sampson’s comment on wheat allergy in Asia (2004):• I was absolutely fascinated by what you and Motohiro

(Ebisawa) are seeing about wheat allergy in Asia

ACCURATE DIAGNOSIS OF FOOD ALLERGY

• History only is not sufficient• Only 30% of OFC will be positive (Bock – J Ped 90)

• Even lower number among current situation (Fleischer – J Ped 2011)

• Elimination diet may not be COMPLETELY reliable particularly for non-IgE reactions

• Oral food challenge – gold standard – increase QOL of patients and family

• OFC vs DBPCFC (Open food challenge vs Double-blind, placebo-controlled food challenge)

• DBPCFC is usually indicated in older children

• Young children learns to avoid shape of the ‘offending food’ and ‘refuse to take them’• DBPCFC – becomes the ‘NECESSARY TOOL’

QUALITY OF LIFE AND RESULTS OF DBPCFC

• 221 patients (age 8-50 years) undergoing DBPCFC were studied

• HRQL were completed before and 6 mosafter challenge

• Risk for accidental exposure

• Emotion

• Restriction of diet and FAIM

• FA-related health

• Significant improvement in HQRL among those with negative challenges

• Less with positive challenges

• No change among the control group

Adults

Children

Teenagers

Vander Velde J et al.J Allergy Clin Immunol 2012;130:1136-43.

Case#4,A 27-year-old marine (male) with history of anaphylaxis for 5 times within the past 5 years. A 27-year-old male soldier has had 5 episodes of the following

symptoms Eye itching, swelling progressing to urticarial all over the body.

Difficulty to breath, wheezing

Abdominal pain and vomiting

In one episode, there was hypertension and cyanosis.

No relationship between episodes and of exercise. He has had allergic rhinitis for a while.

He noted that in 1 episode, it occurred after eating some local fried chicken and on another pieces of baked bakery.

What will be your approach in this patient?

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Pancake syndrome (Anaphylaxis after food contaminated with house-dust mites)

Initial report in 1993 in a patient who ingested beignet (special pastries) made from dough contaminated with house-dust mites.

Symptoms include

Itching of face, swelling of eye lids

Difficulty of breathing, wheezing.

Vomiting, abdominal pain

Hypotension – frank anaphylaxis

Believed to be caused by heat-resistant mite allergens.

No challenge has been performed.

Treatment – avoidance and adrenaline

Sanchez-Borges et al. World Allergy Organization Journal 2009;2:91-6

• 13 patients identified, 6-died and 7-near fatal required intubation

• All had asthma• All were precipitated by consumption of allergic foods

• 4-peanuts, 6-nuts, 1-egg, 1-milk• Among 6 who died only 2 had epinephrine injections• Courses of anaphylaxis

• progressive -7• biphasic – 3• protracted - 3

PEANUT HYPERSENSITIVITY

• Most common allergen associated

with anaphylaxis and death

worldwide

• Less common found in Asia

RISING PROBLEMS WITH PEANUT IN ISLE OF WIGHT 1986-96

0

0.5

1

1.5

2

2.5

3

3.5

Reported peanut reactions SPT positive ot peanuts

1986

1996

Percent

Grundy et al. J Allergy Clin Immunol 2002;110:784

PEANUT BUTTER – FOODLANDPinklao

Accessed SEPTEMBER 5, 2014

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PEANUT HYPERSENSITIVITY IN THAI CHILDREN

• 19 peanut allergic Thai children –

• Male predominance 73%

• Age of onset 24 months

• Only 24% was born in the US

• Co-sensitization to grass 64%, soy

21%

• Wheal size of > 8 mm increased OR

• Specific IgE to Ara h2 – predicted

reactions

Suratannon et al. Pediatr Allergy Clin 2013;24:665-70

คนไข้ใหม่ของ อ ปกิตเอง

April 14, 2010

Pudding containing peanut

Eating military ration with peanut t school

CLINICAL DEFINITION OF ANAPHYLAXIS

Anaphylaxis – Criteria #2 and #3

2. After exposure to known allergens – to the patients, occurrences of (within minutes to hours)

and 2 or more of the followingsa) History of severe allergic reaction.

b) Hives, generalized itch/flush, swollen lips/tongue/uvula

b) Airway compromise (dyspnead, wheeze/bronchospashm, stridor, reduced PEF)

c) Reduced BP or associated symptoms (eg Hypotonia, syncope)

d) In suspected food allergy: gastrointestinal symptoms (crampy abdominal pain, vomiting

3. Hypotension after a known allergen to that patients (after minutes to hours)a) Infants and children: low systolic BP (age specivic) or >30% drop in systolic BP

b) Adults: systolic BP < 100 mmHg or > 30% drop from baseline

FOODS

Sampson et al. J Allergy Clin Immunol 2005;115:284-91

TREATMENT OF ANAPHYLAXIS

Immediate Action

• Assessment

- AIRWAY – open airway, O2 Sat

- Breathing - O2, mouth piece, bag

- Cardiac – pulse, BP – CPR ready

• Give ADRENALINE 0.3 CC IM in the thigh repeatable q 10-15

min

• Place patient in the supine position with legs elevated

• Give oxygen 2-4 Lt/min

• If the antigen (or other causal agent) has been injected, place a

TOURNIQUET proximal to the injection site

NOT DEXA + CPM injections

2014

• Reported incidence of anaphylaxis is increasing

• Increasing of hospitalization from anaphylaxis was observed

• Food is the major cause of anaphylaxis

• Epinephrine is the DRUG OF FIRST CHOICE for treatment of anaphylaxis

• Epinephrine 1:1000 at dosage of 0.01 mg/kg should be give IM as soon as possible.

• Lack of controlled trial of use of antihistamines in anaphylaxis treatment

• Corticosteroids has questionable role in anaphylaxis

http://www.eaaci.org/resources/scientific-output/guidelines/2533-food-allergy-and-anaphylaxis-guideline.html - accessed March 22 2015

THE TORMENT OF BEING LABELED ‘FOOD ALLERGIC’

• Feeling of guilt among the patient and parents

• Fear of accidental exposure

• Uncertainty about obtaining food. Difficulty in buying foods

• Cost of food replacement – burden to the low-income family

• Diet restriction – AVOID THE BIG 8!!!! – LIFE IS A MISERY!!!

• Social deletion

• Concern about growth and general well-being

• Depression – anxiety – obsessive compulsive – other neurologic diseases

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Accidental exposures with reactions may occur even after adequate preparation (rate may be up 50% of patients)

Anagnostou et al. Lancet 2014;383(9925):1297-304

THE TORMENT OF FOOD AVOIDANCETHE ‘ACCIDENTAL EXPOSURES’

Ewan and Clark. Lancet 2001;357:111-5

• 567 peanut/nuts allergic patients were followed for – 610 patient-months (median 21)

• Instructions to avoid peanuts with oral antihistamines with/without inhaled or injected epinephrine were given

• 88 (15%) had reactions, 69 were mild, 12 were moderate and 3 were severe

• Most reactions occurred outside the homes –mostly in restaurant – with some patients’acknowledgement of the food content.

AGE OF ONSET OF SHRIMP ALLERGYN = 63 PATIENTS

Mahavijit and Vichyanond 2014 in preparation

SHRIMP ALLERGY AND ANAPHYLAXISIN THAI CHILDREN

60 patients with + history and + SPT

to shrimp were subjected to

challenges• Group I – positive to P monodon 12

(17.6%)

• Group II – positive to M rosenberg – 16

(23.5%)

• Group III – positive to both – 32 (47%)

• Group IV – negative to both – 8 (11.7%)

Paneus monodon(Seawater shrimp)

Macrobrachiumrosenbergii

(Freshwater shrimp)

Jirapongsananurak et al. Clin Exp Allergy 2008; 38:1038–1047

FRUIT HYPERSENSITIVITY SUMMARY

• Food allergy is ‘a second wave of surging allergy epidemic’

• Common foods causing allergy are EGGS, MILK, WHEAT, SEAFOOD, PEANUTS

• FOOD ALLERGY CAN CAUSE DEATH FROM ANAPHYLAXIS

• Epinephrine – ADRENALINE IS THE FIRST CHOICE OF ANAPHYLAXIS TREATMENT

Not CPM or DEXA

• Treatment of food allergy

• Avoidance

• Rx when symptoms develop

• Oral immunotherapy in those whose age range exceeds possibility of remission

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•ลกูฉนัจะหายจากโรคแพ้อาหารนีไ้หม??

• เม่ือไรลกูฉนัจะหายจากโรคแพ้อาหารนีส้กัที ??

•คณุหมอจะช่วยให้ลกูฉนัหายได้ไหม?? ด้วยวิธีไหน??

GROWING OUT OF FA = GAINING OF NATURAL TOLERANCE

NATURAL HISTORY OF COW MILK ALLERGY –CONSORTIUM OF FOOD ALLERGY – COFAR -USA

• 244 children with CMA + egg + AD from 5 different sites in the USA were followed

• Outcome – when will the child tolerate milk?

• 154 children (52.4%) tolerated milk at median of 63 months (5 yrs 3 mos)

• Predictors were Sp IgE to milk, SPT to milk and severity of atopic dermatitis

• The ‘Milk Calculator’ – www.cofargroup.org

Wood RW et al. J Allergy Clin Immunol 2013;131:805-12

Resolution of milk allergy as a function of SpIgE to milk

NATURAL HISTORY OF EGG ALLERGY IN CHILDREN CONSORTIUM OF FOOD ALLERGY – COFAR -USA

• 213 children with egg allergy + milk + AD

from 5 sites in the USA were followed

• Outcome = resolution of egg allergy

• 105 (49.3%) children tolerated egg at age 72

months (6 years)

• Predictors = SpIgE to egg, SPT egg, AD

severity, IgG4 and IL-4 response

• The ‘Egg Calculator’ – www.cofargroup.org

Resolution of egg allergy as a function of SpIgE to egg

Sicherer SH et al. J Allergy Clin Immunol 2014;133:492-9

The CoFAR ‘MILK Calculator’

http://www.cofargroup.org/

The CoFAR ‘Egg Calculator’

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COULD WE ACCELERATE THE OCCURRENCE OF FOOD TOLERANCE?

TOLERANCE INDUCTION IN FA

JJ Allergy Clin Immunol 1999;99:744-51

1.Active

2.

2. Passive

RUSH SCIT TO PEANUT – DBPCFC RESULTS

Active RxControl

Nelson et al. J Allergy Clin Immunol 1999;99:744-51

ANTI-IGE IN PEANUT ALLERGY

Leung et al. N Engl J Med 2003;348:986-93

CAN WE DO ORAL IMMUNOTHERAPY??

• Wuthrich B. Oral desensitization with cows milk in cows milk allergy. Pro! In: Wuthrich B, Ortolani C, editors. Highlights in food allergy. Basel, Karger,Monogr Allergy, 1996, 32: 236–240.

• Patriarca G, et al. Food allergy in children: results of a standardized protocol for oral desensitization. Hepatogastroenterology 1998;45:52-8.

• Niggemann B, et al. Specific oral tolerance induction in food allergy. Allergy 2006;61:808-11.

• Longo – Milk OIT in severe milk allergic patient – J Allergy Clin Immunol 2008

• Staden. et al. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 2007: 62: 1261–1269.

SPECIFIC ORAL IMMUNOTOLERANCE TO FOOD – CHARITÉ – OSNABRUCK - GERMANY

• Controlled trial for SOTI

• 25 SOTI to milk (14) and egg (11)

• 20 on elimination diet

• Daily induction phase with daily

maintenance dose

• After maintenance of 21 mos

• strict avoidance of 2 mos

• another challenge

• Successful rate: 16/25 SOTI (64%) vs

7/20 Control (35%)

Staden. et al. Allergy 2007: 62: 1261–1269

Lots of minor but annoyance adverse reactionsincluding flare of AD!!!

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Longo et al. J Allergy Clin Immunol 2008;121:343-7

• 97 children > 5 years with severe CMA with SpIgE to CM > 85 KIU/L!!!!

• 30 received CM SOTI and 30 – AA control for 1 year

• Very slow - 10 days – in-hospital rush to reach 20 ml of CM

• Slow home increase for 1 year.

SOTI IN PATIENTS WITH SEVERE CM ALLERGY

Longo et al. J Allergy Clin Immunol 2008;121:343-7

A SIRIRAJ PATIENT WITH SEVERE CM 2008

(+) THE LONGO PROTOCOL

(+) LOTS OF GUTS!!!!!

SOTIed HIM!!!!

All pictures are shown with families’permission

2008 SpIgE CM = 7.5 at 3 years with repeated severe anaphylaxis to milk (respiratory mainy)

SomyingPan

(+)

SomboonBoonNattida

Pang

NongnapaNee Patcharaporn

AnnAll pictures are shown with families’permission

• Start SOTI on July 08• Took about 5 mos to

reach 180 cc• Has been maintaining

on 800 cc/d without any problem

• Most recent SpIgE to CM <0.07

• July 16, 2014

All pictures are shown with families’permission

Accidental Exposure to Cow’s Milk in a Thai Girl 2013

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Egg white = 2/3 of egg weightsEgg yolk = 1/3 of egg weights

1 eggs = 60-70 gm

Burks et al. N Engl J Med 2012;367:233

Prof Hugh Sampson

Prof Wesley Burks

Burks et al. N Engl J Med 2012;367:233-43

• 55 egg allergic children studied, 40 OIT, 15 placebo• Initial induction and maintenance daily phase = 10 mos• Daily maintenance dose = 2 gm egg white = 1/3 egg• 55% of OIT passed DBPCFC at 10 mos. placebo = 0%• Rate of passing increased to 75% at 22 mos (10 gm)• At 24 mos (after stopping OIT for 4-6 wks) only 28%

persistent tolerance (up to 35 mos)• SpIgG4 correlate with tolerance

MULTIPLE FOOD ALLERGY SYNDROME

INDICATIONS OF ORAL IMMUNOTHERAPY (OIT) TO FOOD ESP WHEAT

• Absolute indication (Siriraj 13 – Vichyanond/Pajarn )

1. the Patient is truly allergic (IgE-mediated) to that food with high

SpIgE to that food

2. the Patient’age has exceeded the age of reported occurrence of

natural tolerance – the COFAR calculators

3. Several accidental exposures with serious consequences has

occurred in the past year (3-4 at least – COFAR GRADING 3-4)

4. The Family want to undertake the risk of adverse reaction to food

OIT and also demonstrate to use Epipen at home

SUCCESSFUL ORAL IMMUNOTHERAPY IN TWO VERY HIGHLY SENSITIVE WHEAT ALLERGIC

PATIENTS

TassalapaDang

NantanaJoo

A Koy

WasineeFai

ChulamaneeNing

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NATURAL HISTORY OF WHEAT ALLERGY AMONG 55 THAI CHILDREN

• 55 children with hx of wheat sensitivity and positive SPT and/or SpIgE to wheat

and 5--gliadin was studied

• Challenge performed in 25 children with SpIgE to wheat less than 26 KIU/L and 5-- gliadin < 1.06

• 18 passed challenge – giving tolerance rate of 32.7%

• Median age of tolerance = 76 mos

Siripattanamongkol N, Pacharn P, et al. Submitted 2014

Peak wheat IgE level VS persistence of wheat allergy

Keet et al. Ann Allergy Asthma Immunol2009;102:410-415

THE SIRIRAJ WHEAT ALLERGY TEAM

REMAINING QUESTIONS

• DBPCFC – appropriate protocol – hiding medium –

interpretation – beginning dose – eliciting dose – open dose

• OIT – slow vs rush protocol – day 1 only vs day 1-7 or 10

• Weekly increment – dose

• Maintenance dose – form

• Duration of maintenance

• Repeated challenges

COW’S MILK ALLERGY (CMA) IN ISRAEL

• Largest prospective cohort study for

cow’s milk allergy – 13,090 children

• Verified by challenges

• Prevalence IgE-mediated CM = 0.5%

(prevalence of non-IgE reaction = 0.5%)

• Symptoms: skin (98%), GI (54%), Resp

(27%)

• Early introduction of CM (<2 mos) was

associated with less CMA (> 4 mos) –

OR 19.3 (CI = 6.0-62.1)Katz Y et al. J Allergy Clin Immunol 2010;126:77-82

Pairwise comparison P < 0.001for all groups

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• 2589 one-year-old infants in Melbourne

was studied.

• SPT to egg-white follow with blinded

challenges of raw egg white was

performed

• History of feeding practice was

recorded.

• Group with egg introduced early had

less egg allergy at 1 year of age.

• Protective effect was seen only with

cooked egg but not baked egg.

0

0.5

1

1.5

2

2.5

3

3.5

4

Age egg introduced Age solid introduced Durations of BF

Adjusted OR for egg allergy from Table II

Age 4 mos Age 6 mos Age > 6 ms Age > 12 mos

Early exposure to cooked egg (at 4-6 mos of age) decrease the incidence of egg allergy among 1 -year-old Australian infants

Koplin, et al. J Allergy Clin Immunol 2010;126:807-13

p = 0.16

p < 0.001

p = 0.088

PEANUT ALLERGY

PEANUT IMMUNOTHERAPY – THE GERMAN TRIAL

• 24 peanut allergic (DBPCFC) underwent

peanut OIT targeted at 500 mg

• Targeted OIT dose = 5 gm of crushed

peanut (= 4 small peanut kernels,

125/each)

• 14 passed OIT at 7 months at a median

dose of 1 gm

• Adverse reactions were not serious

Blumchen et al. J Allergy Clin Immunol 2010;126:83-91.

• 99 severe peanut allergic were randomized to receive peanut OIT

• (50 active, 49 control)• Mean age 11 years, mostly males• 50% has eczema, asthma and allergic rhinitis• 26% had other food allergy (milk and egg)• At 26 wks of OIT vs control

• 82% of OIT passed 800 mg DBPCFC (0% in control)

• Increase in peanut consumption tolerated = 25 times

• At 52 weeks, control group which received OIT 54% passed food challenge

PEANUT ORAL IMMUNOTHERAPY IS POSSIBLE!!!!

University of Cambridge, UK

Anagnostou et al. Lancet 2014;383(9925):1297-304

Dutoit et al.

Bamba Peanut Snack

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The LEAP study result – NIAID-sponsored 640 infants with severe eczema and or egg allergy were enrolled

530 infants had SPT positive to peanut

98 infants had already positive SPT to peanuts (< 4 mm wheal)

Age of enrollment – 4 -11 mos

Open-study; peanut consumption – Bamba stick (7 gm/2 weeks) vs none

92% rate of adherence

Consumption vs avoidance

Primary prevention 1% vs 6% (80% reduction)

Secondary prevention 6.8% vs 33.1% (70% reduction)

Safety – no deaths, Side effects were not seriousDutoit et al.

The ‘LEAP’study result 2015(Learning about Peanut Allergy)

Dutoit et al.