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Clinical food challenges 2007 EAACI Göteborg. Ulf Bengtsson Department of Respiratory Medicine and Allergology Sahlgrenska University Hospital Göteborg. Introduction.

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clinical food challenges 2007 eaaci g teborg

Clinical food challenges2007 EAACI Göteborg

Ulf Bengtsson

Department of Respiratory Medicine and Allergology

Sahlgrenska University Hospital

Göteborg

Ulf Bengtsson

introduction
Introduction
  • In many situations, the diagnosis of food allergy rests simply upon a history of an acute onset of typical symptoms, such as hives and wheezing, following the isolated ingestion of a suspected food, with conformatory positive IgE-tests.

Ulf Bengtsson

slide4
Ex.
  • A history of anaphylaxis and pos IgE-tests; here challenges normally are contraindicated!
  • Clear-cut objective symptoms with pos IgE-tests

Ulf Bengtsson

slide6
When multiple foods are implicated
  • In chronic diseases: asthma, atopic dermatitis
  • When reactions are not IgE-mediated (e.g. food related gastrointestinal symptoms)

Ulf Bengtsson

slide7
Elimination diets followed by physician-supervised oral challenges are critical in the identification and proper treatment of these disorders

Ulf Bengtsson

basics for investigation
Basics for investigation

History and IgE-tests

Food challenges

Elimination diets

Ulf Bengtsson

slide11
To exclude food allergy in order to prevent the individual being subjected to unnecessary or even harmful elimination diets

Ulf Bengtsson

slide12

Challenge models

Indication

Labial challenge

In high risk patients? In patients with pronounced fear of special foods?

Screening method?

Titration /stepwise increase of dose,

Open, single blind or DBPCFC.

A history of anaphylaxis

Open challenges with normal portions

The actual history is doubtful

Blinded placebo controlled food challenges-normal portion

Add a food back to the diet under safe conditions

In subjective symptoms- gastrointestinal complaints, atopic eczema

Food aversion, a psychological condition when a person has a reaction, caused by emotions associated with food.

Ulf Bengtsson

slide13

Labial food challenge (LFC)

The method was described by F Rancé, G Datau, France,

PAI 1997; 8: 41-4

Ulf Bengtsson

method
Method
  • Inspect the face and the mouth cavity
  • Place the food inside of the lower lip during 2 minutes.
  • Observe for local or systemic reactions in the ensuing 30 minutes

Ulf Bengtsson

method1
Method

A positive test is:

  • development of a contiguous rash of the cheek and chin
  • oedema of the lip with conjunctivitis or rhinitis
  • systemic reaction

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method2
Method
  • Negative labial food challenges are generally followed by open oral food challenges

Ulf Bengtsson

is lfc an alternative to the other methods
Is LFC an alternative to the other methods?
  • Sensitivity is poor
  • DBPCFC are required after negative LFC results
  • Further comparative anlyses of the LFC and oral challenges will better determine the value of LFC for exploration of cases of food allergy

Ulf Bengtsson

possible indications
Possible indications
  • In high risk patients where food challenges are planned

Ulf Bengtsson

possible indications1
Possible indications
  • Before open challenges in patients with a history of pronounced fear of special foods

Ulf Bengtsson

slide20

LFC

  • Simple
  • Rapid to perform
  • Associated with a low risk of systemic reactions

Ulf Bengtsson

open food challenges
Open food challenges

Indications:

  • Reactions which can be confirmed objectively

Ulf Bengtsson

open food challenges1
Open food challenges
  • For practical reasons, an open challenge can be the first approach when the probability of a negative outcome is estimated to be very high

Ulf Bengtsson

slide23

In infants and children <3 years old, an open, physician- controlled challenge is often sufficient for suspected immediate type reactions.

Open food challenges

Ulf Bengtsson

slide24

Open food challenges

  • For patients with pollen-related oral allergy syndrome (OAS) as their only symptom, an open challenge could be sufficient as regular procedure - due to difficulties in blinding fruits and vegetables concerning their allergenicity

Ulf Bengtsson

slide25

Open food challenges

  • Pollen-related oral allergy syndrome (OAS)

Ulf Bengtsson

summary open food challenges
Characteristics: Fresh food in relevant amount. Can be titrated

Advantages: Easily performed. Negative test makes DBPCFC superfluous

Disadvantages: Risk of false positive results

Summary - open food challenges

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slide27
Single blind placebo- controlled food challenges
  • Double blind placebo-controlled food challenges (DBPCFC)

Ulf Bengtsson

dbpcfc
DBPCFC

Placebo challenges are indicated

  • when expected late phase clinical reaction or day-to-day-variations play a role

Ulf Bengtsson

dbpcfc1
DBPCFC
  • when subjective symptoms may play a role (such as gastrointestinal symptoms, headache or palpitations)

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slide30

DBPCFC

  • DBPCFC is the method of choice for scientific protocols.

Ulf Bengtsson

dbpcfc with capsules or tablets
Characteristics: Dehydrated food

Advantages: Can be titrated, commercially available

Disadvantages: Many capsules, reactions in mouth and throat not diagnosed, food quality unknown

DBPCFC with capsules or tablets

Ulf Bengtsson

dbpcfc with masked vehicle
DBPCFC with masked vehicle
  • Characteristics: Fresh food in relevant amount.

Can be titrated and given via tube or masked vehicle

  • Advantages: Quantity of allergen. Reactions in mouth diagnosed. Normal route of administration.
  • Disadvantages:Resource-demanding, not standardized

Ulf Bengtsson

confusing factors1
Confusing factors
  • Physical exercise
  • Drugs (acetylsalicylic acid, beta-blockers, angiotensine-converting enzyme), alcohol
  • Fat content
  • Hormonal factors
  • Psychologicol factors

Ulf Bengtsson

food dependent exercise induced anaphylaxis
Food-dependent exercise-induced anaphylaxis
  • Food-dependent exercise-induced anaphylaxis is revealed by a chronological sequence in which food intake, followed by exercise, induces symptoms after a varying period.
  • When the food intake and the exercise are independent of each other, there are no symptoms.

Ulf Bengtsson

food dependent exercise induced anaphylaxis1
Food dependent exercise induced anaphylaxis
  • In food-dependent exercise-induced anaphylaxis (FDEIA) it is difficult to mimic all parameters in the challenge procedure

Ulf Bengtsson

food dependent exercise induced anaphylaxis2
Food dependent exercise induced anaphylaxis
  • In the challenge procedure it may be important to standardize exercise with and without the suspected food

Ulf Bengtsson

slide38

Interplay between food allergens,

aspirin and exercise

  • Aspirin enhances the induction of IgE- allergic symptoms when combined with foods and exercise in patients with food-dependent exercise-induced anaphylaxis.
  • Harada S et al. Br J Dermatol 2001; 145: 336-9

Ulf Bengtsson

food challenges and fat content
Food challenges and fat content

The fat content of a challenge vehicle may effect the reaction pattern experienced after allergen ingestion.Grimshaw KE et al. Clin Exp Allergy 2003; 33: 1581-5 van Odijk J, Bengtsson U. et al. Allergy 2005; 60: 602-5

Ulf Bengtsson

food challenges and fat content1
Food challenges and fat content
  • If you have a low (normal) fat content you may have reactions to a smaller dose and earlier onset of symptoms
  • If you have a high fat content the reactions are delayed and more pronounced perhaps because more foods are eaten before the reactions occurs.

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slide41
Problems…..

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there are no general agreements about
There are no general agreements about
  • The amount of foods to use
  • How to hide taste, smell and colour
  • Time between separate challenges
  • Increase of dose
  • How to deal with patients with a history of food intolerance after days or weeks of regular intake of suspected foods (delayed reactions)
  • False negative test

Ulf Bengtsson

general agreement
General agreement
  • Patients with manifest, life-threatening symptoms or anaphylaxis should not be challenged

Ulf Bengtsson

however
However……..

Ulf Bengtsson

slide45

DBPCFCs in children with a history of ana- phylaxis to foods: Are they necessary and safe?BJ Vlieg-Boerstra, Groningen, Netherlands, AAAAI San Diego 2007

  • 22 children with a clear-cut history of anaphylaxis to foods were double blind challenged
  • 16 were DB positive, 5 were negative (23%) and 1 was questionable.

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slide46
So perhaps, in selected cases with a history of food related anaphylaxis, we should challenge to avoid unnessesary elimination diets

Ulf Bengtsson

specific ige and dbpcfc
Specific IgE and DBPCFC
  • Allergy tests on their own cannot be considered diagnostic when approximately 10% of DBPCFC, although positive, do not correlate with immunoglobuline E-mediated disease.

Ulf Bengtsson

slide48
A special problem in adults is patients with a history of IBS-like symptoms. The prevalence of IBS in the western world is 20%. >60% of these patients have a history of food related abdominal symptoms mainly because of unspecific visceral hypersensitivity.

Ulf Bengtsson

slide49
The prevalence of IBS in the western world is 20%
  • >60% of these patients have a history of food related gastrointestinal symptoms

Ulf Bengtsson

slide50
In recent years several papers have been published indicating a specific hypersensitivity in subgroups of IBS-patients despite lack of food specific IgE in skin or serum.

Ulf Bengtsson

slide51
Studies supporting a local allergic GI reaction in DB-positive patients lacking systemic food-specific IgE
  • Bengtsson U et al. Gut 1996; 39: 130-135
  • Bischoff SC et al. Gut. 1997 Jun;40(6):745-53
  • Bengtsson U et al. J Allergy Clin Immunol 1997; 100: 216-21
  • Lin XP et al. J Allergy Clin Immunol 2002; 109: 879-87
  • Arslan G et al. Digestion 2006; 73 :111-115..

Ulf Bengtsson

slide52

Double-blind placebo-controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms Bengtsson U et al. Gut 1996; 39: 130-135.

  • 96 consecutive patients with food related gastrointestinal symptoms
  • 41 pat. had pos open challenges
  • 36 pat. participated in DBPCFC
  • 15 pat. had DBPCFC pos challenges
  • None had specific IgE-antibodies against the responsible food

Ulf Bengtsson

slide53
1997 S Bischoff published a heroic study in DB-pos patients with food related gastrointestinal symptoms. He made a pricktest i ileum and could show pos PT in patients lacking specific IgE in skin or serum.

Ulf Bengtsson

slide54

Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergyBischoff S et al, Gut. 1997 Jun;40(6):745-53

  • CONCLUSION:
    • Antigen induced weal and flare reactions were correlated with intestinal mast cell and eosinophil activation, as well as with patients\' history of adverse reactions to food, but not with specific IgE in skin or serum.

Ulf Bengtsson

slide55

Intestinal inflammation assessed by immunohistochemical investigation of duodenal biopsies after food challengesLin XP, J Magnusson, S Ahlstedt A Dahlman-Höglund, L Å Hanson, O Magnusson, U Bengtsson, E Telemo. Local allergic reaction in food hypersensitive adults, despite lack of systemic food-specific IgE. J Allergy Clin Immunol 2002; 109: 879-87

Ulf Bengtsson

case report arslan g et al digestion 2006 73 111 115
Case report Arslan G et al. Digestion 2006; 73 :111-115.
  • A food hypersensitivity reaction was visualised by ultrasonography and magnetic resonance in a patient lacking systemic food-specific IgE
  • Ultrasonsgraphy and magnetic resonance indicated intestinal wall thickning and influx of large amounts of fluids into the proximal small intestine within 10 minutes after egg challenge. The response was associated with abdominal pain and bloating.

Ulf Bengtsson

slide57
So, in a subgroup of patients with a history of food related gastrointestinal symptoms mimicing irritable bowel syndrom may have a specific food allergy/intolerance despite of negative IgE-tests in skin or serum

Ulf Bengtsson

dbpcfc2
DBPCFC
  • DBPCFC is considered as the gold standard
  • DBPCFC also acts as the reference test when a new test is being evaluated

Ulf Bengtsson

dbpcfc3
DBPCFC
  • Consequently, we cannot evaluate the reference test against the gold standard since these are the same tests.
  • Furthermore, the accuracy of DBPCFC depends on how it is conducted and how the results are interpreted.

Ulf Bengtsson

slide61

DBPCFC

  • Thus, DBPCFC is not evidence based and its accuracy is unknown
  • Frustrating, since estimates of prevalence of allergy to different kinds of food depend up on the accuracy of the test

Ulf Bengtsson

slide62

DBPCFC

  • Since most of the developed theory of diagnosing food allergy relies of the assumption that DBPCFC has high accuracy, this accuracy must be formally statistically evaluated.

Ulf Bengtsson

the next slide is a pater published by m gellerstedt et al
The next slide is a pater published by M Gellerstedt et al.
  • It is important to develop precise standards for collection and interpretation of subjective symptoms to achieve as high reproducibility as possible
  • He has shown that a systematic approach of interpreting symptoms can give high interobserver reability even i case of vague symptoms like gastrointestinal pain

Gellerstedt M, Bengtsson U et al. Allergy 2004; 59: 354-356

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slide64

Interpretations of subjective symptoms in double blind placebo controlled food challenges-Inter-observer-reability.Gellerstedt M et al. Allergy 2004; 59: 354-356

Ulf Bengtsson

subjective symptoms
Subjective symptoms
  • To confirm that subjective reactions are de facto associated with the food tested or not, several provocations must be used, at least 5 provocations
  • This is necessary due to the fact that the proportion of positive placebo provocations may be as high as 35%.

Bindslev-Jensen C. Curr Probl Dermatol. 1999; 28: 74-80

Gellerstedt M et al. Allergy 2004; 59: 354-356

Ulf Bengtsson

position paper from the european academy of allergology and clinical immunology
Position paper from the European Academy of Allergology and Clinical Immunology
  • Standardization of food challenges in patients with immediate reactions to foods
  • Bindslev-Jensen C et al Allergy 2004 Jul;59(7):690-7

Ulf Bengtsson

position paper from the european academy of allergology and clinical immunology1
Position paper from the European Academy of Allergology and Clinical Immunology
  • Standardization of food challenges in patients with subjective or delayed reactions to foods
  • This paper is desirable but is not yet written!

Ulf Bengtsson

dbpcfc4
DBPCFC
  • It is desirable to further improve the diagnostic work up of the patients and to valuate if the DBPCFC could, in the diagnostic work up, be replaced by alternative tests.

Ulf Bengtsson

conclusion
Conclusion
  • In clinical practice, elimination diet and food challenge is the best way to give a correct diagnos in a patient with a history of food related symptoms with or without pos IgE-tests.

Ulf Bengtsson

slide70

Cow´s milk allergy -History and IgE-tests often enough, sometimes challenges

Peanut anaphylaxis-

history and IgE tests

enough

Peri-oral dermatitis-citrous fruits-

a convincing history

often enough

Lactose intolerance-a convincing history

often enough, sometimes challenges

Biogenic amines (e.g. histamine)-a convincing history

often enough

Peanut-

butter

MILK

Food related gastrointestinal symptoms-

open or blinded challenges

Tuna

Additives-open or blinded

challenges

Ulf Bengtsson

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