Sami Bahna, MD, DrPHProfessor of Pediatrics & Medicine

Chief of Allergy & Immunology Section

Louisiana State University

Health Sciences Center

Shreveport, Louisiana

SBAHNA@LSUHSC.EDU

WISC, Dubai, Dec 2010

• MEDICAL HISTORY: Nature & course of symptoms, feeding

history, relation of symptoms to eating or to other factors

• PHYSICAL EXAMINATION: Signs of allergy or other diseases

• INITIAL LABORATORY TESTS:

To exclude nonallergenic disease

To support allergy diagnosis (IgE; eosinophils)

• SCREENING TESTS FOR FOOD ALLERGENS:

SPT; specific IgE Ab; trials of elimination diets; diaries

• VERIFICATION : Elimination – challenge test

Food Allergy Diagnosis

Medical history± Skin testing± Specific IgE

Suspected foods

Strict elimination trial

Symptoms improved

Challenge test

Equivocal symptoms

Definite symptoms

No symptoms

OFFENDING FOOD

Symptoms not improved

Food reintroduced

No change

Symptoms worsened

INNOCENT FOOD

Single-blind Double-blindOpen

A. Open Food Challenge

• Food is given in its usual form.

• Both the observer & the patient know.

• Acceptable in infants & young children with

objective symptoms.

• Preliminary screening of foods that are at a low

level of suspicion.

B. Single-Blind Food Challenge• Food should be well disguised (color,

texture, odor, taste).

• Appropriate placebo.

• Observer knows but not the patient.

• Tests must be administered in the same way.

• Result is revealed to the patient after all

challenges are done.

• Applicable to most cases in clinical practice.

C. Double-Blind Food Challenge• Food is well disguised (color, texture, odor, taste).

• Neither observer nor patient knows.

• Food & placebo prepared & coded by a third person.

• Test substances are given in a random fashion,

exactly in the same way.

• After all challenges are done, code is opened &

results are discussed.

• Ideal for research & for some cases in clinical

practice.

How reliable is the medical history

in food allergy diagnosis?

Reactions to Foods & AdditivesEstimated Prevalence

• Claimed by 20-30% of people. These are self-diagnosed perceived reactionsto foods; highly over-estimated!

• True (confirmed) food allergy:6-7% in children1-2% in adults

Manifestations in 4 patients with confirmed

food allergy out of 23 who claimed so(Pearson et al: Lancet 1:1259, 1983)

Urticaria 4

Allergic rhinitis 4

Bronchial asthma (2 immediate & 1 late-onset) 3

Atopic dermatitis 2

Abdominal pain 2

Symptoms attributed to “food allergy” by 19 patients

in whom food allergy was not confirmed(Pearson et al: Lancet 1:1259,1983)

Symptoms No. %Lethargy or feeling unwell 16 84

Head pain or tightness 13 68

Abdominal swelling or discomfort 10 53

Depression 10 53

Bowel disturbance 9 47

Paraesthesia 9 47

Nausea 8 42

Palpitation 8 45

Abdominal pain or heartburn 7 37

Threshold

Psychiatric score in patients presenting with suspected food allergy

(Pearson et al: Lancet 1983, 1:1259)

Your problem isn’t

something you ate.

It is something you

married.

How reliable is skin testing in

food allergy?

Skin Test Reliability Compared to

Double-Blind Oral Challenge to Food

Cow Egg

Skin test reliability % Total* milk Crab white Fish Peanut Shrimp

Sensitivity (true positive test) 57.9 44.4 66.7 66.7 83.3 66.7 62.5

Specificity (true negative test) 65.2 66.7 60.0 80.0 50.0 57.1 75.0

Positive predictive accuracy 47.8 66.7 33.3 50.0 83.3 40.0 71.4

Negative predictive accuracy 73.8 44.4 85.7 88.9 50.0 80.0 66.7

* Include figures on several foods, which are not presented individually because of small numbers

Predictive SPT wheal diameter of positive

challenge to egg & milk in children______________________________________________________________________________________________________________________________________

Predictive SPT diameter (mm)

level < 1 yr > 1yr

Hen egg 90% 9.3 11.1

95% 11.2 13.3

99% 15.4 18.3

n = 26 n = 134

---------------------------------------------------------------------------

Cow milk 90% 7.9 13.2

95% 9.7 15.799% 13.5 *

n = 154 n = 149

* could not be calculated. (Modified from Verstege et al. Clin Exp Allergy 2005; 35:1220)

Skin prick test result compared with food challenge outcome.

(Nolan et al: Ped Allergy Immunol 2007,18:224)

Positive challenge

Negative challenge

How reliable is sIgE testing in

food allergy?

sIgE (RAST) Reliability Compared to

Double-Blind Oral Challenge to Foods

Cow Egg

RAST reliability % Total* milk Crab white Fish Peanut Shrimp

Sensitivity (true positive test) 58.3 55.6 66.7 33.3 100 75.0 62.5

Specificity (true negative test) 33.4 66.7 40.0 40.0 0.0 28.6 37.5

Positive predictive accuracy 43.7 71.4 25.0 14.3 71.4 37.5 50.0

Negative predictive accuracy 67.4 50.0 80.0 66.7 0.0 66.7 50.0

* Include figures on orange, tomato and soy, which are not presented individually because of small numbers

Predictive Value of Food-Specific IgE

by CAP-FEIA in Children with

Atopic Dermatitis(Sampson & Ho: JACI 1997; 100:444)

Food PPV 90% PPV 95%

Egg 2 KU/L 6 KU/L

Peanut 9 KU/L 15 KU/L

Fish 9.5 KU/L 20 KU/L

Milk 23 KU/L 32 KU/L

Soy Best PPV was 50%, at 65 IU/ml

Wheat Best PPV was 75%, at 100 IU/ml

Probability curves for food reaction according to sIgE

immunoCAP in a prospective vs a retrospective study (1997)(Sampson : JACI 2001; 107:891)

Probability curves for food reaction according to sIgE immunoCAP

in a prospective vs a retrospective study (Sampson & Ho1997)(Sampson : JACI 2001; 107:891)

6

Probability curves for food reaction according to sIgE immunoCAP

in a prospective vs a retrospective study (Sampson & Ho1997)(Sampson : JACI 2001; 107:891)

32

Probability curves for food reaction according to sIgE immunoCAP

in a prospective vs a retrospective study (Sampson & Ho1997)(Sampson : JACI 2001; 107:891)

15

Probability of positive egg challege according to sIgE (ImmunoCAP) in

children (0.2-14.6yr); mostly AD (74%)(Komata et al: JACI 2007;119:1272)

Egg

Probability of positive milk according to sIgE (ImmunoCAP) in

children (0.2-14.6yr); mostly AD (74%)(Komata et al: JACI 2007;119:1272)

Milk

sIgE levels with 95% predictability of

positive challenge by age (Komata et al: JACI 2007, 119:1272)

Age Egg Milk

< 1 yr 13 KU/L 5.8 KU/L

1 to < 2 yr 23 KU/L 38.6 KU/L

2 yr + 30 KU/L 57.3 KU/L

(sIgE by Immuno-CAP system)

What is the best cut-off of milk-sIgE level?(Garcia-Ara et al, J Allergy Clin Immunol, 2001)

Specific IgE interpretation

Factors to be considered:

• Total IgE level

• Patient’s age

• Type of allergy manifestation

• Severity of allergy manifestation

• Food allergen

• Degree of exposure to the food

• Duration of avoidance of the food

Why Food Challenge?

• Verification of the diagnosis of food allergy.

• Identification of the truly offending food(s).

• Limiting the dietary elimination, which would:

- Improve the quality of life.

- Enhance the compliance with diet.

- Prevent potential mal- or under-nutrition.

• Exclusion of food allergy would allow further

investigation for other causes of the symptoms.

Positive Double-Blind Food Challenge in 10 Studies

Author Population Children Adults

Positive DBFC

Foods Patients May ’76

Aas ’78

Ford & Fergusson ’80

Sampson ’87

Bock ’86

Sampson ’88

Bernestein et al ’82

Atkins et al ’85

Onoreto et al ’86

Bahna & Gandhi ’87

Range

Average

X

X

X

X

X

X

X

X

X

X

X

X

14/70

119/446

26/54

22/104

96/431

180/514

13/46

12/71

13/35

38/107

533/1878

(20%)

(27%)

(26%)

(21%)

(22%)

(35%)

(28%)

(17%)

(37%)

(36%)

(17-37%)

(28%)

11/38

-

26/40

14/26

81/206

98/160

10/22

10/24

11/20

36/61

297/597

(29%)

-

(65%)

(54%)

(39%)

(61%)

(45%)

(42%)

(55%)

(59%)

(29-65%)

(50%)

(Modified from Pastorello et al. Allergy Proceeding 1991;12:319)

Should food allergy be always

confirmed by challenge?

In instances where a specific food has

caused a life-threatening reaction,

particularly if more than once,

food challenge in any form is

contraindicated.

(If necessary, skin or labial contact may be done)

Let’s get out of here.