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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



Ex.

  • A history of anaphylaxis and pos IgE-tests; here challenges normally are contraindicated!

  • Clear-cut objective symptoms with pos IgE-tests

Ulf Bengtsson



Ulf Bengtsson


Ulf Bengtsson


Basics for investigation
Basics for investigation challenges are critical in the identification and proper treatment of these disorders

History and IgE-tests

Food challenges

Elimination diets

Ulf Bengtsson


The aims of controlled food challenges are
The aims of controlled food challenges are: challenges are critical in the identification and proper treatment of these disorders

Ulf Bengtsson



Ulf Bengtsson


Challenge models being subjected to unnecessary or even harmful elimination diets

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


Labial food challenge (LFC) being subjected to unnecessary or even harmful elimination diets

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

PAI 1997; 8: 41-4

Ulf Bengtsson


Method
Method being subjected to unnecessary or even harmful elimination diets

  • 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 being subjected to unnecessary or even harmful elimination diets

A positive test is:

  • development of a contiguous rash of the cheek and chin

  • oedema of the lip with conjunctivitis or rhinitis

  • systemic reaction

Ulf Bengtsson


Method2
Method being subjected to unnecessary or even harmful elimination diets

  • 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? being subjected to unnecessary or even harmful elimination diets

  • 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 being subjected to unnecessary or even harmful elimination diets

  • In high risk patients where food challenges are planned

Ulf Bengtsson


Possible indications1
Possible indications being subjected to unnecessary or even harmful elimination diets

  • Before open challenges in patients with a history of pronounced fear of special foods

Ulf Bengtsson


LFC being subjected to unnecessary or even harmful elimination diets

  • Simple

  • Rapid to perform

  • Associated with a low risk of systemic reactions

Ulf Bengtsson


Open food challenges
Open food challenges being subjected to unnecessary or even harmful elimination diets

Indications:

  • Reactions which can be confirmed objectively

Ulf Bengtsson


Open food challenges1
Open food challenges being subjected to unnecessary or even harmful elimination diets

  • 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


Open food challenges

Ulf Bengtsson


Open food challenges controlled challenge is often sufficient for suspected immediate type reactions.

  • 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


Open food challenges controlled challenge is often sufficient for suspected immediate type reactions.

  • 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

Ulf Bengtsson


Ulf Bengtsson


Dbpcfc
DBPCFC titrated

Placebo challenges are indicated

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

Ulf Bengtsson


Dbpcfc1
DBPCFC titrated

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

Ulf Bengtsson


DBPCFC titrated

  • DBPCFC is the method of choice for scientific protocols.

Ulf Bengtsson


Dbpcfc with capsules or tablets

Characteristics: Dehydrated food titrated

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 titrated

  • 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 factors

Confusing factors….. titrated

Ulf Bengtsson


Confusing factors1
Confusing factors titrated

  • 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 titrated

  • 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 titrated

  • 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 titrated

  • In the challenge procedure it may be important to standardize exercise with and without the suspected food

Ulf Bengtsson


Interplay between food allergens, titrated

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 titrated

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 titrated

  • 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.

Ulf Bengtsson


Ulf Bengtsson


There are no general agreements about
There are no general agreements about titrated

  • 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 titrated

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

Ulf Bengtsson


However
However…….. titrated

Ulf Bengtsson


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.

Ulf Bengtsson


Ulf Bengtsson


Specific ige and dbpcfc
Specific IgE and DBPCFC anaphylaxis, we should challenge to avoid unnessesary elimination diets

  • 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


Ulf Bengtsson


  • The prevalence of IBS in the western world is 20% 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.

  • >60% of these patients have a history of food related gastrointestinal symptoms

Ulf Bengtsson


Ulf Bengtsson


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


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


Ulf Bengtsson


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


Intestinal inflammation assessed by approach for gastrointestinal food allergyimmunohistochemical 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 approach for gastrointestinal food allergyArslan 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


Ulf Bengtsson


Critical aspects of dbpcfc

Critical aspects of DBPCFC 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 gastrointestinal symptoms mimicing irritable bowel syndrom may have a specific food allergy/intolerance despite of negative IgE-tests in skin or serum

  • 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 gastrointestinal symptoms mimicing irritable bowel syndrom may have a specific food allergy/intolerance despite of negative IgE-tests in skin or serum

  • 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


DBPCFC gastrointestinal symptoms mimicing irritable bowel syndrom may have a specific food allergy/intolerance despite of negative IgE-tests in skin or serum

  • 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


DBPCFC gastrointestinal symptoms mimicing irritable bowel syndrom may have a specific food allergy/intolerance despite of negative IgE-tests in skin or serum

  • 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. gastrointestinal symptoms mimicing irritable bowel syndrom may have a specific food allergy/intolerance despite of negative IgE-tests in skin or serum

  • 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

Ulf Bengtsson


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 placebo controlled food challenges-

  • 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 Clinical Immunology

  • 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 Clinical Immunology

  • 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


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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