Standardizationoffoodchallengesinpatientswithimmediate ...

1 Review articleStandardization of food challenges in patients with immediatereactions to foods position paper from the European Academyof Allergology and Clinical ImmunologyAt present, the double blind placebo controlled foodchallenge (DBPCFC) represents the only way to establishor rule out an adverse reaction to a food in older childrenand adults, whereas an open challenge controlled bytrained personnel is sufficient in infants and youngchildren (1). The challenge procedure is not, however,C. Bindslev-Jensen1, B. K. Ballmer-Weber2, U. Bengtsson3, C.

2 Blanco4,C. Ebner5, J. Hourihane6,A. C. Knulst7, D. A. Moneret-Vautrin8,K. Nekam9, B. Niggemann10,M. Osterballe1, C. Ortolani11,J. Ring12, C. Schnopp13, T. Werfel141 Allergy Center, Odense University Hospital,Odense, Denmark;2 Allergy Unit, Department ofDermatology, University Hospital Zurich, Zurich,Switzerland;3 The Asthma and Allergy ResearchGroup, Department of Respiratory, Medicine andAllergy, Sahlgrenska University Hospital,Gothenburg, Sweden;4 Secci*n de Alergia,Hospital Dr Negr,n, Las Palmas de , Spain;5 Allergieambulatorium, Wien, Austria;6 WellcomeTrust Clinical Research Facility, SouthamptonUniversity Hospitals NH STrust, Southampton, UK.

3 7 Department of Dermatology/Allergology, UniversityMedical Center Utrecht, Utrecht, The Netherlands;8 Intern Medicine, Clinical Immunology andAllergology, Hospital Central, Nancy, France;9 Department of Allergy and Clinical Immunology,Polyclinic of the Hospitaller Brothers of St. John ofGod, Budapest, Hungary;10 Department of PediatricPneumology and Immunology, University Children'sHospital Charit>, Berlin, Germany;11 Allergy/ClinicalImmunology, Niguarda Ca'Granda, Milan, Italy;12 Department of Dermatology and Allergology,Technische Universit?t M@nchen, Munich, Germany;13 Division Environmental Dermatology andAllergology GSF/TUM, Department Dermatology andAllergy Biederstein, Technische Universit?

4 TM@nchen, Munich, Germany;14 Department ofDermatology and Allergology, Haut Klinik Linden,Hannover Medical University, Hannover, GermanyCarsten Bindslev-JensenAllergy CenterOdense University HospitalDK5000 OdenseDenmarkAccepted for publication 23 November 2003 Allergy 2004: 59: 690 697 Printed in UK. All rights reservedCopyright Blackwell Munksgaard 2004 ALLERGY690fully developed and no standardised procedure has so farbeen agreed upon, although a manual describing severalof the issues has previously been published (2). For thesafety and feasibility of the patient undergoing challengethere is a need for standardisation of the also allows for comparison of resultsbetween different centers and different populations inscientific protocols.

5 This Position Paper gives advice onhow the procedures can be performed, but since there areno direct comparative studies available in the literaturedirectly comparing the various parameters ( timingbetween two subsequent challenges or increment of thedose for challenge) we have not been able to recommendtruly evidence based guidelines. It is also important torealize, that legislative aspects vary in different countrieswithin Europe, and that the guidelines presented hereinmust be adjusted according to local legislation. Further-more this guideline does not constitute a guideline forEthics Committees to decide feasibility of DBPCFC in ascientific are several issues to be determined, prior tocommencing a challenge in a patient.

6 These can be dividedinto patient-related parameters, which are parametersconcerning the actual patient in question and procedure-related parameters, which deal with the parametersindependent of the patient in question (Table 1).Selection of patients for challengeChallenge should be performed either for establishmentor exclusion of the diagnosis, for scientific reasons inclinical trials or for enabling determination of thesensitivity of the actual patient (threshold value) or fordetermining the allergenicity of foods. The determinationof the sensitivity both enables tailor-made guidelines forthe patient and opens the possibility of following sensi-tivity by repeated challenges especially in children withfood allergies normally outgrown during childhood(cow s milk or hen s egg).

7 Patients should be investigated according to theEAACI guidelines (1) using case history combined within vivoandin vitrotesting supplemented with a elimin-ation diet period prior to challenge when necessary. Basedon the findings here, the patient-related parameters canbe guidelines in this position paper focus mainly onpatients presenting classical immediate type allergicsymptoms and signs (IgE-mediated type I allergy), asdefined in EAACI position paper (1).Inclusion criteriaPatients of any age with a history of adverse reaction to afood: For establishment or exclusion of the diagnosis of foodintolerance/allergy For scientific reasons in clinical trials For determination of the threshold value or degree ofsensitivity For assessment of tolerance.

8 Once diagnosed, when apatient is suspected to have outgrown his clinicalallergy especially in children, whose food allergiesnormally outgrow during childhood, cow s milk orhen s egg without specific history of adverse reaction to afood: If any chronic symptom is suspected by the patient orthe physician to be food-related If a patient is on an improper elimination diet - with-out history of adverse food reaction , the food has tobe reintroduced and there are reasons for suspectingthat an adverse reaction is possible. If a sensitization to a food is diagnosed and tolerance isnot known for example, sensitization to cross-react-ive foods that have not been eaten after the patients for DBPCFC include:1.

9 All patients with suspicion of an immediate, systemicallergic reaction to a food for establishment or exclu-sion of the diagnosis2. in infants and children three years, an open chal-lenge controlled and evaluated by a physician is mostoften Patients with pollen related oral allergy syndrome (5)as their only symptom should only undergo DBPCFC outside scientific protocols in selected cases; forexample in cases with discrepancy between case historyand outcome ofin vivoand/orin open challenge may precede DBPCFC in olderchildren and adults because a negative result hereinrenders DBPCFC unnecessary.

10 Open challenges shouldnot be applied in cases with a high probability of aTable related parameters age of the patient clinical features of the suspected reaction severity of the reaction dosing (start dose, increment, top dose) timing between challenges regimen (in-patient or out-patient) special considerations (concomitant factors)such as a possible influence of concomitantexercise (3) or intake of drugs such asb-blockers, ACE-inhibitors or aspirin (4), alcohol,antihistamines, corticosteroidsProcedure related parameters settings (trained personnel) safety measures informed consent procedures blinding procedure statistical evaluationFood allergy challenge procedures691positive outcome or in cases with subjective and/orcontroversial symptoms only (6).