- Email: [email protected]
Food allergy and pseudoallergy
REVUEFRAN~AISE
30
D ALLERGOLOGIE
ETD'IMMUNOLOGIECLINIQUE
Food allergy and pseudoallergy T. WERFEL
The diagnosis of f o o d allergy appears to increase in clinical practice. The cause may be that many patients or their parents now attribute complaints to foods due to the popularity of this diagnosis. Two criteria have to be fulfilled by definition in food allergy: (i) a specific senzitization and (ii) clinical symptoms which occur after the ingestion of f o o d allergens. Pseudoallergy which will be discussed at the end of this paper mimics food allergy without specific senzitization to the f o o d stuff which causes clinical problems.
FOOD
ALLERGY"
GENERAL
ASPECTS
The following elements may lead to the diagnosis of food allergy: - Anamestic data - Skin tests - I n vitro tests - Elimination diets - Provocation tests. The mainstay in the therapy of food allergy is an elimination diet. Symptomatic therapy has often to be prescribed since the elimination of certain
Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, 30449 HANNOVER.
food stuff can be extremely difficult in everydays practice. Immune therapy can be used if a crossreaction to pollen allergens exists. HOW FOOD
OFTEN
ALLERGY
DOES OCCUR?
The relation between food allergy and suspected food allergy varied in different studies between 4:1 and 10:1. The question of an objective increase of food allergy is still open since suspected food allergy is difficult to be differentiated in epidemiological studies. In studies using oral provocation tests a prevalence of food allergy was calculated to be 6 % in infants and children and to vary between 1 and 2 % in adults [1, 8]. This means that food allergy is i n d e e d a relative c o m m o n and i m p o r t a n t problem in allergological practice. Crossreactive foods which show structural similarities to inhalant allergens (pollen, latex) have probably led to an objective increase of food allergies during the last decades [8]. Pollen associated foods such as nuts, apples, celery or carrots commonly led to immediate symptoms in sensitized patients which are restricted to the oral region in most patients (so-called oral
WERFEL T. - Food allergy and pseudoallergy. Rev. fr. Allergel., 1999, (Numero special), 30-33.
© Expansion Scientifique Publications, 1999
31
/FOOD ALLERGY AND PSEUDOALLERGY °
allergy syndrome). The same holds true for latex associated foods such banana, m a r o n e or avocado. Rarely, dangerous reactions including anaphylactic reactions have been described for these foods as well. Moreover, late reactions such as the deterioation of atopic dermatitis have been observed and investigated in detail recently [14].
and out-patient clinics rather than in surgeries due to practical reasons [20]. If a positive result is observed u p o n oral provocation the elimination diet should be continued. For some food stuffs (e.g. cow's milk) the provocation t e s t should be repeated once a year in children due to the high rate of spontaneous tolerance.
CLINICAL SYMPTOMS IN F O O D ALLERGY
FURTHER DIAGNOSTIC PROCEDURES
The clinical spectrum of food allergy is broad: Both immediate symptoms (urticaria, flush, allergic asthma bronchiale, rhinitis allergica and gastro-intestinal symptoms) and delayed symptoms (gastrointestinal, c u t a n e o u s e.g. worsening of atopic dermatitis) can be observed [1, 8, 17]. Delayed symptoms are difficult to be diagnosed since an exact attribution of clinical symptoms to the ingestion of a certain food stuff can be impossible [21, 24]. Other symptoms such as the induction of serous otitis media (which may be caused indirectly by tubular obstruction due to food induced rhinitis), migraine or psychological symptoms are still controversely discussed with respect to food allergy. So far no double blind placebo controlled oral food challenge studies have been published which might have prooved an association of the latter diseases and food allergy [12].
DIAGNOSTIC PRINCIPLES
The allgorithm in the diagnosis of food allergy has been outlined by two current position papers: The European Academy of Allergology, Asthma and Clinical Immunology (EAACI) has published their position in 1995 and the interest group of food allergy of the German society of Allergology and Immunology (DGAI) has published their proposals in 1998 [1, 11]. Due to both papers the anamnesis should be followed by in vitro tests (i.e. specific IgE) or skin tests (prick tests). The most c o m m o n mistake is t h a t sensitization is considered as food allergy. This is not true since 2 / 3 of all sensitized individuals do not react to oral provocation with the corresponding food stuff [16]. T h e r e f o r e the next step should be the performance of an elimination diet for some weeks [2] with a subsequent oral provocation. The "gold standard" in the diagnostics of food allergy is a double blind placebo controlled oral food challenge which is usually p e r f o r m e d in inRev.fr. AIlergoI., 1999, Num6ro special
Current studies evaluate the predictive and diagnostic values of cellular in vitro tests such as the lymphocyte stimulation test, the basophil histamine release test or the basophil leukotrien release test. Moreover, the eosinophilic parameters ECP and EPX which may be used for an objective diagnosis of food allergy ar still under study. The lymphocyte stimulation test may lead to satisfying results if contaminating lipopolysaccharides are eliminated from food allergens prior to their addition to the cell cultures [13, 22, 23]. This expensive and time consuming p r o c e d u r e cannot be p e r f o r m e d by many laboratories. Therefore the lymphocyte stimulation test cannot be r e c o m m e n d e d for the c o m m o n diagnosis of food allergy. A recently evaluated "'new" instrument which might be suitable for the indication of a sensitization of food i n d u c e d eczema in children's atopic dermatitis is the patch test p e r f o r m e d with native food stuff [7, 15]. This test should, however, not replace oral provocation tests. A n u m b e r of procedures are used for the diagnosis of food allergy which are of no value such as the d e t e r m i n a t i o n of specific IgG, cytoxiticity tests or bioresonsance tests.
PROCEDURES IN SUSPECTED PSEUDO-ALLERGIC REACTIONS
Pseudo-allergic reactions resemble allergic reactions and patients with chronic urticaria, recurring angioedema, polyposis nasi or nonallergic bronchial asthma (intrinsic asthma) suffer from pseudo-allergic reactions m o r e frequently. Food-ingredients are considered as pseudo-allergens besides non-steroidal antiphlogistica and other drugs which can cause symptoms in sensitive patients [3, 9, 18]. There is no clear knowledge a b o u t the frequency of pseudo-allergic reactions. The published frequency of pseudo-allergic reactions to food ingredients ranged from less than 1% to over 50 % in chronic urticaria [4, 5, 9, 10, 18, 26].
32
• T. TA~RFEL /
A defined pseudoallergen can be identified in only a small subgroup of patients whose symptoms improve during an elimination diet [5, 6. 9, 18]. In contrast to allergic reactions to foods there are still no in vitro or skin tests available for the identification of pseudo-allergen which is relevant for a patient. It was possible, however, to detect a hyperreactivity of basophils and eosinophils in response to unspecific stimuli in pseudo-allergic individuals compared to healthy persons [3, 4, 19]. The used test systems do not allow, however, to identify a specific cause of a clinical reaction. Elimination diets and oral provocations have always to be p e r f o r m e d to identify clinically relevant pseudoallergens. One has to differentiate between a specific investigation of a particular pseudo-allergen (e.g. in the case of a tartrazine intolerance, associated with a known acetylic acid intolerance [18]), and a rather unspecific investigation in the case of chronic urticaria or chronic angio-edema. The latter situation is more c o m m o n in clinical practice and is briefly outlined.
RECOMMENDED DIAGNOSTIC PROCEDURES IN CHRONIC URTICARIA AND SUSPECTED FOOD INTOLERANCE
Elimination diets avoiding foods with high concentrations of biogenic amines (histamin, tyramin and others), preservatives, food dies and anti-oxydants should be performed for three to four weeks [6]. If no improvement is observed, the interest group of food allergy of the DGAI recommends an oligo-allergenic basic diet over an additional period of 5-7 days [15, 25]. If no improvement can be observed during the diet and the subsequent oligo-allergen-diet a triggering of the symptoms by pseudo-allergence is not probable and further provocation-tests should n o t be performed. Oral provocations should usually be performed in hospital. There should be no angioedema at the beginning of the tests. No drugs, which may influence the clinical reaction may be given during the time of testing. As mentioned above, food additiva do usually n o t lead to positive oral provocation tests if given seperately. Therefore a subsequent provocation with salicylates, benzoates, sulfites, and antioxydants is not r e c o m m e n d e d in chronic urticaria by the DGAI group. Provocation tests with pseudo-allergen-rich meals should be performed instead over the period of 2 days [25].
If no clinical reactions are observable, pseudoallergent-rich meals should be given for two further days. If the patient reacts, a second period with elimination diets has to be p e r f o r m e d with subsequent provocations with food additiva. If pseudo-allergen rich meals lead to positive reactions only, a slow normalisation of the diet, adding new foods every 3 days, can be tried. Ideally, an individual therapeutical diet can be r e c o m m e n d e d at the end of this process. In case of a positive reacuon upon combined provocation with pseudo-allergens, or if a particular pseudo-allergen is under suspect (e.g. sulfides as trigger factors of respiratory obstruction), a double-blind oral provocation with individual substances should be performed. In the case of severe clinical reactions, a titration of these substances is recommended. Only one group of substances should be given per day because late reactions may occur.
THERAPEUTICAL ASPECTS IN FOOD ALLERGY
The elimination of food allergens and pseudoallergens can be difficult. On reason is that there are still serious legal problems in the full declaration of foods in the European union and in other countries. Celery for example is seldom indicated as "celery" in composed foods. Instead celery may still be hidden as "spice" in the decleration of such food which of course does not help an individual who is allergic to celery. Children may become tolerant to their food allergen. Cow's milk'leads to tolerance in more than 90 % of all children who developed milk allergy during the first year of life [8]. Therefore it is important that children do not stick too long on a cow's milk free elimination diet as mentioned [11]. Soy bean and hen's egg also lead quiet commonly to tolerance in contrast to peanut, fish or nuts. Oral and subcutaneous i m m u n e therapy is being discussed as therapy for food allergic patients as well. 50 % of pollen allergic patients will improve with respect to their food allergy upon specific i m m u n e therapy with the corresponding cross reactive inhalant allergen. Subcutaneous i m m u n e therapy with food extracts is not established. Oral desensitization therapy may be applied in some cases. There are, however, no controlled studies available for this therapy bearing the potential risk of severe side effects if the daily therapy is interrupted by the patient [8]. Rev.fr. AllergoL, 1999, Num6ro sp6cial
33
/ FOOD ALLERGY AND PSEUDOALLERGY •
Antihistamines, cromoglycine and steroids are the most c o m m o n drugs which are available for the symptomatic therapy of food allergy. A period of six m o n t h breast feeding is still r e c o m m e n d e d for the prevention of allergic symptoms in allergic families. Extensive protein hydrolysates can be used as an alternative if breast feeding is not possible or sufficient. Maternal diets during the breast feeding period are still controVersely discuss-
ed. Maternal diets during gravidity cannot be r e c o m m e n d e d due to the results of current studies. Finally it is very important to point out that there are no established diets for a certain diagnosis (e.g. a diet suitable for all patients suffering from atopic dermatitis). In contrast, the relevance of an individual sensitization has to be found out in each patient to avoid elimination diets which will not help the patient.
REFERENCES 1. Bruijnzeel-Koomen C., Ortolani C., Aas IL, Bindslev-Jensen C., Bjorksten B., Moneret-Vautrin D., Wfithrich B. - Allergy" Adverse reactions to food. European Academy of Allergology and Clinical Immunology Subcommittee. 1995, 50 : 623-35. 2. Czech W., Busse A., Wedi B., Kapp A. - Nahrungsmitteladditiva u n d nichtsteroidale Anfiphlogistika - Ausl6ser von pseudoallergischen Reakfionen. Allergologie 1996, 19 : 442-448. 3. Czech W., Sch6pf E., Kapp A. - Release of sulfidoleukotrienes in vitro: Its relevance in the diagnosis of pseudoallergy to acetylsalicylic acid. Inflamm Res 1995; 44: 291-295. 4. Douglas H.M.G. - Reactions to aspirin and food additives in patients with chronic urticaria, including physical urticarias. Br J Dermatol 1975; 93: 135-144. 5. Ehlers I., Hertz B.M., Zuberbier T. - Diagnose u n d Therapie pseudo-allergischer Reaktionen der Haut durch Nahrungsmittel. Allergologie 1996; 19:270-276. 6. Constien A., Werfel T., Kapp A. - Praktische Aspekte zur Efn~hrungstherapie bei Nahrungsmittelallergien u n d -intoleranzen. In: Bachert C, H e p p t W (Hrsg): Praktische Allergologie. Thieme Verlag, 1998, 131-37. 7. Isolanri E., Turjanmaa K. - Combined skin prick and patch testing enhances identification of food allergy in infants xdth atopic dermatitis. J Allergy Clin Immunol. 1996, 97 : 9-15. 8. Jfiger L.; Wfithrich B. - Nahrungsmittelallergien u n d - intoleranzen. Fischer Verlag, 1998. 9. Metcalfe D.D., Sampson H.A., Simon R.A. - Food allergy. Adverse reactions to foods and food additives. Blackwell, Oxford London, 1996 (2. Auflage). 10. Michaelsson G.,Juhlin L. - Urticaria induced by preservative and dye additives in food and drugs. BrJ Dermatol 1973 ; 88 : 525-532. 11. Niggemann B., Kleine-TebbeJ., SalogaJ., SennekampJ., VielufI., Vieths S., WerfeI T., JSger L. - Standardisierung von oralen Provokationstests bei IgE-vermittelten Nahrungsmittelallergien. AllergoJ 1998, 7: 45-50. 12. Ortolani c., Bruijnzeel-Koomen C., Bengtsson U., BindslevJensen C., Bjorksten B., Host A., Ispano M, Jarish R., Madsen C., Nekam IC, Paganelli R., Poulsen L.K., Wuthrich B. - Controversial aspects of adverse reactions to food. Allergy 1999, 54: 27-45. 13. Reekers R, Beyer K, Niggemann N., Walm U., FreihorstJ., Kapp A., WerfeI T. - The role of circulating food antigen specific lymphocytes in food allergic children with atopic dermatitis. BrJ Dermatol 1996, 135: 935-41.
mmm
Rev.fr. Allergol., 1999, Num6ro sp6cial
14. Reekers R., Busche M., Wittmann M., Kapp A., Werfel T. - Birch pollen related food trigger atopic dermatitis with specific cutaneous T-cell responses to birch pollen antigens. J Allergy Clin Immunol 1999, (in press). 15. Reibel S., Niggemann B., Wahn U. - Der Atopie Patch Test (APT) in der Diagnostik yon Nahrungsmittelallergien im Kindesalter. AllergoJ 1999, 8: 21. 16. Sampson H.A., Albergo R. - Comparison of results of skin tests, RAST, and double blind, placebo-controlled food challenges in children with atopic dermatitis. J All Clin Immunol 1984, 74, 26-33. 17. Sampson H.A., McCaskill C.C. - Food hypersensitivity and atopic dermatitis: Evaluation of 113 patients. J Pediatr 1985, 107, 69-675. 18. Simon R.A., Stevenson D.D. -Adverse reactions to food and drug additives. In: Allergy, Principles and Practice. 4. Auflage. Middleton E, Reed CE, Ellis EF et al. (eds.). Mosby, St. Louis, U.S.A. 1993, 168%1704. 19. Wedi B., ElsnerJ., ILapp A. - In vitro diagnostic of pseudo-allergic reactions - New aspects. ACI International 1996, 8 : 113-115. 20. Werfel T. - Indikation, Technik, Aussagewert u n d Risiken der oralen Provokation bei allergischen u n d pseudoallergischen Reaktionen. In: Meigel W, Moll I, Plettenberg H: Dermatologie an der Schwelle zum neuen Jahrtausend. Springer Verlag, 1999 (in press). 21. Werfel T. - Die Rolle yon Nahrungsmittelallergenen als Provokationsfaktoren der atopischen Dermatitis. In: Meigel W, Moll I, Plettenberg H : Dermatologie an der Schwelle zum neuen Jahrtansend. Springer Verlag 1999 (in press). 22. Werfel T., Ahlers G., Schmidt E, Boeker M., Kapp A. - Detection of a K-casein specific lymphocyte response in milk-responsive atopic dermatitis. Clin Exp Allergy 1996, 26: 1380-6. 23. Werfel T., Ahlers G., Schmidt E, Boeker M., Kapp A., N e u m a n n C. - Milk-responsive atopic dermatitis is associated with a caseinspecific lymphocyte response in adolescent and adult patients. J Allergy Clin Immunol 1997, 99: 124-33. 24. Werfel T., Kapp A. - Environmental and other major provocation factors in atopic dermatitis. Allergy 1998, 53: 73t. 25. Werfel T., Wedi B., Kleine-Tebbe J., Niggemann B., Saloga J., Sennekamp J., Vieluf I., Vieths S., Zuberbier T., J/iger L. Vorgehen bei Verdacht auf eine pseudoallergische Reaktion auf Nahrungsmittelinhaltssmffe. AllergoJ 1999, 8: 135-141. 26. Zuberbier T., Chantraine-Hess S., Hartmann IL, Czarnetzki B.M. - Pseudoallergen-free diet in the treatment of chronic urticaria. Acta Derm Venereol (Stockh) 1995 ; 75 : 484-487.
30
D ALLERGOLOGIE
ETD'IMMUNOLOGIECLINIQUE
Food allergy and pseudoallergy T. WERFEL
The diagnosis of f o o d allergy appears to increase in clinical practice. The cause may be that many patients or their parents now attribute complaints to foods due to the popularity of this diagnosis. Two criteria have to be fulfilled by definition in food allergy: (i) a specific senzitization and (ii) clinical symptoms which occur after the ingestion of f o o d allergens. Pseudoallergy which will be discussed at the end of this paper mimics food allergy without specific senzitization to the f o o d stuff which causes clinical problems.
FOOD
ALLERGY"
GENERAL
ASPECTS
The following elements may lead to the diagnosis of food allergy: - Anamestic data - Skin tests - I n vitro tests - Elimination diets - Provocation tests. The mainstay in the therapy of food allergy is an elimination diet. Symptomatic therapy has often to be prescribed since the elimination of certain
Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, 30449 HANNOVER.
food stuff can be extremely difficult in everydays practice. Immune therapy can be used if a crossreaction to pollen allergens exists. HOW FOOD
OFTEN
ALLERGY
DOES OCCUR?
The relation between food allergy and suspected food allergy varied in different studies between 4:1 and 10:1. The question of an objective increase of food allergy is still open since suspected food allergy is difficult to be differentiated in epidemiological studies. In studies using oral provocation tests a prevalence of food allergy was calculated to be 6 % in infants and children and to vary between 1 and 2 % in adults [1, 8]. This means that food allergy is i n d e e d a relative c o m m o n and i m p o r t a n t problem in allergological practice. Crossreactive foods which show structural similarities to inhalant allergens (pollen, latex) have probably led to an objective increase of food allergies during the last decades [8]. Pollen associated foods such as nuts, apples, celery or carrots commonly led to immediate symptoms in sensitized patients which are restricted to the oral region in most patients (so-called oral
WERFEL T. - Food allergy and pseudoallergy. Rev. fr. Allergel., 1999, (Numero special), 30-33.
© Expansion Scientifique Publications, 1999
31
/FOOD ALLERGY AND PSEUDOALLERGY °
allergy syndrome). The same holds true for latex associated foods such banana, m a r o n e or avocado. Rarely, dangerous reactions including anaphylactic reactions have been described for these foods as well. Moreover, late reactions such as the deterioation of atopic dermatitis have been observed and investigated in detail recently [14].
and out-patient clinics rather than in surgeries due to practical reasons [20]. If a positive result is observed u p o n oral provocation the elimination diet should be continued. For some food stuffs (e.g. cow's milk) the provocation t e s t should be repeated once a year in children due to the high rate of spontaneous tolerance.
CLINICAL SYMPTOMS IN F O O D ALLERGY
FURTHER DIAGNOSTIC PROCEDURES
The clinical spectrum of food allergy is broad: Both immediate symptoms (urticaria, flush, allergic asthma bronchiale, rhinitis allergica and gastro-intestinal symptoms) and delayed symptoms (gastrointestinal, c u t a n e o u s e.g. worsening of atopic dermatitis) can be observed [1, 8, 17]. Delayed symptoms are difficult to be diagnosed since an exact attribution of clinical symptoms to the ingestion of a certain food stuff can be impossible [21, 24]. Other symptoms such as the induction of serous otitis media (which may be caused indirectly by tubular obstruction due to food induced rhinitis), migraine or psychological symptoms are still controversely discussed with respect to food allergy. So far no double blind placebo controlled oral food challenge studies have been published which might have prooved an association of the latter diseases and food allergy [12].
DIAGNOSTIC PRINCIPLES
The allgorithm in the diagnosis of food allergy has been outlined by two current position papers: The European Academy of Allergology, Asthma and Clinical Immunology (EAACI) has published their position in 1995 and the interest group of food allergy of the German society of Allergology and Immunology (DGAI) has published their proposals in 1998 [1, 11]. Due to both papers the anamnesis should be followed by in vitro tests (i.e. specific IgE) or skin tests (prick tests). The most c o m m o n mistake is t h a t sensitization is considered as food allergy. This is not true since 2 / 3 of all sensitized individuals do not react to oral provocation with the corresponding food stuff [16]. T h e r e f o r e the next step should be the performance of an elimination diet for some weeks [2] with a subsequent oral provocation. The "gold standard" in the diagnostics of food allergy is a double blind placebo controlled oral food challenge which is usually p e r f o r m e d in inRev.fr. AIlergoI., 1999, Num6ro special
Current studies evaluate the predictive and diagnostic values of cellular in vitro tests such as the lymphocyte stimulation test, the basophil histamine release test or the basophil leukotrien release test. Moreover, the eosinophilic parameters ECP and EPX which may be used for an objective diagnosis of food allergy ar still under study. The lymphocyte stimulation test may lead to satisfying results if contaminating lipopolysaccharides are eliminated from food allergens prior to their addition to the cell cultures [13, 22, 23]. This expensive and time consuming p r o c e d u r e cannot be p e r f o r m e d by many laboratories. Therefore the lymphocyte stimulation test cannot be r e c o m m e n d e d for the c o m m o n diagnosis of food allergy. A recently evaluated "'new" instrument which might be suitable for the indication of a sensitization of food i n d u c e d eczema in children's atopic dermatitis is the patch test p e r f o r m e d with native food stuff [7, 15]. This test should, however, not replace oral provocation tests. A n u m b e r of procedures are used for the diagnosis of food allergy which are of no value such as the d e t e r m i n a t i o n of specific IgG, cytoxiticity tests or bioresonsance tests.
PROCEDURES IN SUSPECTED PSEUDO-ALLERGIC REACTIONS
Pseudo-allergic reactions resemble allergic reactions and patients with chronic urticaria, recurring angioedema, polyposis nasi or nonallergic bronchial asthma (intrinsic asthma) suffer from pseudo-allergic reactions m o r e frequently. Food-ingredients are considered as pseudo-allergens besides non-steroidal antiphlogistica and other drugs which can cause symptoms in sensitive patients [3, 9, 18]. There is no clear knowledge a b o u t the frequency of pseudo-allergic reactions. The published frequency of pseudo-allergic reactions to food ingredients ranged from less than 1% to over 50 % in chronic urticaria [4, 5, 9, 10, 18, 26].
32
• T. TA~RFEL /
A defined pseudoallergen can be identified in only a small subgroup of patients whose symptoms improve during an elimination diet [5, 6. 9, 18]. In contrast to allergic reactions to foods there are still no in vitro or skin tests available for the identification of pseudo-allergen which is relevant for a patient. It was possible, however, to detect a hyperreactivity of basophils and eosinophils in response to unspecific stimuli in pseudo-allergic individuals compared to healthy persons [3, 4, 19]. The used test systems do not allow, however, to identify a specific cause of a clinical reaction. Elimination diets and oral provocations have always to be p e r f o r m e d to identify clinically relevant pseudoallergens. One has to differentiate between a specific investigation of a particular pseudo-allergen (e.g. in the case of a tartrazine intolerance, associated with a known acetylic acid intolerance [18]), and a rather unspecific investigation in the case of chronic urticaria or chronic angio-edema. The latter situation is more c o m m o n in clinical practice and is briefly outlined.
RECOMMENDED DIAGNOSTIC PROCEDURES IN CHRONIC URTICARIA AND SUSPECTED FOOD INTOLERANCE
Elimination diets avoiding foods with high concentrations of biogenic amines (histamin, tyramin and others), preservatives, food dies and anti-oxydants should be performed for three to four weeks [6]. If no improvement is observed, the interest group of food allergy of the DGAI recommends an oligo-allergenic basic diet over an additional period of 5-7 days [15, 25]. If no improvement can be observed during the diet and the subsequent oligo-allergen-diet a triggering of the symptoms by pseudo-allergence is not probable and further provocation-tests should n o t be performed. Oral provocations should usually be performed in hospital. There should be no angioedema at the beginning of the tests. No drugs, which may influence the clinical reaction may be given during the time of testing. As mentioned above, food additiva do usually n o t lead to positive oral provocation tests if given seperately. Therefore a subsequent provocation with salicylates, benzoates, sulfites, and antioxydants is not r e c o m m e n d e d in chronic urticaria by the DGAI group. Provocation tests with pseudo-allergen-rich meals should be performed instead over the period of 2 days [25].
If no clinical reactions are observable, pseudoallergent-rich meals should be given for two further days. If the patient reacts, a second period with elimination diets has to be p e r f o r m e d with subsequent provocations with food additiva. If pseudo-allergen rich meals lead to positive reactions only, a slow normalisation of the diet, adding new foods every 3 days, can be tried. Ideally, an individual therapeutical diet can be r e c o m m e n d e d at the end of this process. In case of a positive reacuon upon combined provocation with pseudo-allergens, or if a particular pseudo-allergen is under suspect (e.g. sulfides as trigger factors of respiratory obstruction), a double-blind oral provocation with individual substances should be performed. In the case of severe clinical reactions, a titration of these substances is recommended. Only one group of substances should be given per day because late reactions may occur.
THERAPEUTICAL ASPECTS IN FOOD ALLERGY
The elimination of food allergens and pseudoallergens can be difficult. On reason is that there are still serious legal problems in the full declaration of foods in the European union and in other countries. Celery for example is seldom indicated as "celery" in composed foods. Instead celery may still be hidden as "spice" in the decleration of such food which of course does not help an individual who is allergic to celery. Children may become tolerant to their food allergen. Cow's milk'leads to tolerance in more than 90 % of all children who developed milk allergy during the first year of life [8]. Therefore it is important that children do not stick too long on a cow's milk free elimination diet as mentioned [11]. Soy bean and hen's egg also lead quiet commonly to tolerance in contrast to peanut, fish or nuts. Oral and subcutaneous i m m u n e therapy is being discussed as therapy for food allergic patients as well. 50 % of pollen allergic patients will improve with respect to their food allergy upon specific i m m u n e therapy with the corresponding cross reactive inhalant allergen. Subcutaneous i m m u n e therapy with food extracts is not established. Oral desensitization therapy may be applied in some cases. There are, however, no controlled studies available for this therapy bearing the potential risk of severe side effects if the daily therapy is interrupted by the patient [8]. Rev.fr. AllergoL, 1999, Num6ro sp6cial
33
/ FOOD ALLERGY AND PSEUDOALLERGY •
Antihistamines, cromoglycine and steroids are the most c o m m o n drugs which are available for the symptomatic therapy of food allergy. A period of six m o n t h breast feeding is still r e c o m m e n d e d for the prevention of allergic symptoms in allergic families. Extensive protein hydrolysates can be used as an alternative if breast feeding is not possible or sufficient. Maternal diets during the breast feeding period are still controVersely discuss-
ed. Maternal diets during gravidity cannot be r e c o m m e n d e d due to the results of current studies. Finally it is very important to point out that there are no established diets for a certain diagnosis (e.g. a diet suitable for all patients suffering from atopic dermatitis). In contrast, the relevance of an individual sensitization has to be found out in each patient to avoid elimination diets which will not help the patient.
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