iagnosis of food allergy by the radioallergosorbent test Y. Y. Chua, M.D., K. Bremner, BSc., J. 1. Llobet, M.D., H. 1. Kokubu, and C. Collins-Williams, M.D. Toronto, Ontario, Canada

The radioallergosorbent test (RAST) was positive in 5%59$o of 250 sera representing 200 food hypersensitivities from 108 patients with a history of definite immediateCorresponding prick test was performed for 170 of the sem. type reactions to f00a.3. The latter test was positive in 70%, the RAST was positive in SS~~, and either prick test OT RAST was positive in 74a/,. It is concluded that the RAST is positive less frequently than the prick test +n the diagnosis of immediate-type food allergy in clinicrally sensitive patients, but that the performance of both tests increases slightly the possibility of confirming the diagnosis. However, the RAST is useful for fwrther evaluating positive prick tests with foods that do not correlate with dinid hypersensitivity.

Food allergy in children is a sufficient problem to justify investigation for improved methods of diagnosisl, 2 and can produce demonstrable pathologic changes.3 Many children have acute, severe reactions that can often be demonstrated to be associated with a reaginic mechanism, generally assumed but seldomly proved to be IgE-mediated. The present method of study, by history plus skin testing, is not ideal in specific diagnosis because, although a positive prick test often supports a diagnosis of clinical sensitivity, false positives and false negatives are common. Positive intradermal tests, particularly, are irrelevant to the clinical history in many cases, Elimination diets are often necessary for confirmation of the diagnosis, * but these are very troublesome for the patient. Furthermore, many foods are sold as mixtures, confusing the evaluation of clinical reactions, and about 2,700 additives are in common use, many of which are known to be allergenic5 In addition, alleged food allergies are more numerous than true food allergies, with the result that many children are raised on inadequate diets without sufficient evidence to support the dietary restriction-and it is often difficult to convince the parents that the forbidden foods may safely be reintroduced into the diet. Therefore, a reliable laboratory test would be helpful to corroborate the diagnosis of hypersensitivity reactions to food, even though it may never make dietary manipulation unnecessary. In a previous study,6 including 72 of the present sera, we found histamine From the Allergy Division, The Hospital for Sick Children, Toronto, and the Department Paediatrics, University of Toronto. Supported in part by a grant from the Ontario Society for Crippled Children. Received for publication Dec. 2, 1975. Accepted for publication Feb. 13, 1976. Reprint requests to: Dr. C. Collins-Williams, Department of Paediatrics, The Hospital Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.

of

for

Pal. 58, No. 4, pp. 477-482

Chua

et

al.

release from human and monkey lung less often positive patients than the radioallergosorbent test (RAST) , which positive than the prick test. The purpose of the present further the value of the R,AST, an in vitro technique in allergy.‘> *

J. ALLERGY CLIN. IMMUNOL. OCTOBER 1976

in clinically sensitive in turn was less often study was to explore the diagnosis of food

ATIENTS Of the 108 patients studied, 98 were 18 yr of age or less (average, 9.4 yr) and 10 were over 18 (average, 24.4 yr). All had had definite clinical symptoms of hypersensitivity reactions to one or more foods, with or without positive skin tests. All but one of the patients had had symptoms ranging from acute urticaria or angioedema, nausea, vomiting, and diarrhea, to wheezing and shock, starting within 4 hr (usually A = 4+). RAST scores of 2+, 3+, and 4+ were recorded as positive. To determine reproducibility of the RAST, duplicate determinations were repeated in suecessive runs with several food antigens and the same sera (shrimp, 6 runs; peanut, 4 runs; salmon, 4 runs; lobster, 6 runs; cashew, 6 runs). Succ&sive determinations gave reproducible results (SD for binding = approximately 10%) for each antigen. test As additional controls from this same group of patients, 100 positive and 100 negative prick tests associated with a negative clinical history of reaction to food antigens were correlated with the RAST results. For each allergen studied, at least one positive RAST was included with the batch of discs, to confirm that the discs were satisfactory.

Of the 200 sera subjected to RAST, 105 were positive (Table I). These patients had experienced their last clinical reaction up to 15 pr previously. When

Chua

J. ALLERGY CLIN. IMMiJNOL. OCTOBER 1476

et al.

TABLE 111.Correlation History

among

clinical

history,

skin test, and RAST

Prick test

RAST

4%

2%

10’0% 100%

10’0%

100%

100%

+*

14%

These studies were done on the same group of patients, showing that if a given patient was clinically sensitive to a food, the R.AST had a 52% chance of being positive; on the other hand, if the patient was not clinically sensitive to a food but had a positive skin test with that, food, the RAST was less likely to be positive, and if the patient was not clinically sensitive and had a negative skin test, the RAST was almost always negative. “14 allergens in 11 patients. t3 allergens in 1 patient.

we excluded the 120 sera from the patients whose last clinical reaction had occurred more than 1 yr before blood was drawn, the percentages positive for eggs, fish, and nuts were higher, but the overall figures were unchanged. Table II compares results of skin test and RAST (170 hypersensitivities). Positive skin tests in 118 were associated with positive RAST in 89. Fortyfive were negative to both, 7 with a positive RAST had a negative skin test, and 36 with a positive skin test had a negative RAST ; 125 (74%) had a positive skin test or positive RAST. Thus, of 170 immedia.te-type reactions to foods studied (for which skin tests were associated), 70% were associated with positive prick tests and 52% with a positive RAST. By contrast, in the same patient group the RAST was positive in only 14% (11 patients) of tests associated with 100 positive prick tests for which there was no clinical correlation and in only 3% (1 patient) of tests associated with 100 negative prick tests for which there was a negative clinical history (Table III).

Aas and Johansson12 studied 11 patients with cod allergy and found a COF relation between positive RAST and a positive history in 91% of cases. Aas and Lundkvist,13 who performed RAST with a purified allergen from codfish, found 100% correlation between positive RAST and clinical allergy to cod in 56 children, but the RAST was negative in a further 56 who were allergic but who tolerated fish. That these correlations are much higher than ours is explained by the fact that they were using a much purer allergen than is available for most food studies. Hogarth-Scott and co-workers,14 who studied 28 subjects by skin test and RAST with egg albumin, showed correspondence, predominantly negative/negative correlations, in 18 (64%) ; 4 had positive/positive findings, the skin test slightly underscoring the RAST. Nine had a negative skin test response with a low-score positive RAST, indicating greater sensitivity (p < 0.05) of the RAST than the skin test to egg albumin. In contrast, our study, using multiple foods, showed the skin test to be the more sensitive of the two. Foucard, Aas, and Johansson15 studied 15 sera from 13 children with cod-induced asthma and

VOLUME 58 NUMBER 4

Diagnosis of food allergy

found significant correlation (p < 0.001) between R.AST, P-K reaction, and histamine release from human lung; R,AST and P-K had similar positivity, histamine release was less sensitive, and direct scratch tests showed less agreement. The difference from our results is again probably because a highly purified allergen was being used. Hoffman and HaddadlG used the RAST to study sera from 127 children who had experienced at least one episode of immediate hypersensitivity-type symptoms (urticaria, angioedema, anaphylaxis, asthma, allergic rhinitis, and atopic dermatitis) or acute gastrointestinal manifestations after the ingestion of one or more foods. As antigens, they used 14 foods (codfish, cows’ milk, peanut, orange, egg white, wheat, chocolate, walnut, tomato, corn, almond, shrimp, bivalves, and oat), as well as two purified cows’ milk fractions (a-lactoglobulin and ,@lactoglobulin) . They demonstrated specific IgE antibodies to the clinically suspected food allergen in 59% of all reported untoward reactions and a positive RAST to at least one food allergen in 75% of the patients, and therefore concluded that this technique is a useful adjunct in the diagnosis of IgE-mediated food hypersensitivity. Their findings are very similar to ours. Schur, Hyde, and Wypych17 studied 34 children with atopic eczema, comprising 13 clinically sensitive (group 1) and 21 not clinically sensitive (group 2) to egg white. In group 1, RAST levels were between 00/o and 2470 in 2 patients, 25% and 100% in 6, and exceeded 100% in 5, but prick skin tests to egg white were positive in only 5. In group 2, RAST levels were 070 to 2470 in 17 and exceeded 100% in only 1, and the prick test was positive in only 3 of the 21 patients. The egg white RAST showed significant correlation with clinical egg sensitivity (p = 0.0005) and with prick skin test with the same antigen (p = 0.036)) but clinical egg sensitivity did not correlate with the egg white skin test. The last disagrees with our findings of a high correlation (70%) between clinical sensitivity and skin test. Our results suggest that many immediate-type adverse reactions to foods are IgE-mediated ; all of the patients have histories compatible with this diagnosis. Prick tests were positive for 70% of the 170 hypersensitivities for which they were performed, and the R’AST was positive in 52.5v0 of the total 200 sera. The percentage of positive RASTs was unaffected by time elapsed (up to 15 yr) since the last clinical reaction to the food, indicating that the production of specific IgE continues for a very long time, if not indefinitely. The prick test is a useful diagnostic tool, being more sensitive than the RAST in immediate-type food allergy in clinically sensitive patients. In addition, the incidence of a positive RaST with a negative clinical history but positive skin test is much lower, indicating the value of the RAST in invalidating false positive prick tests to foods which are important in the diet but which the patient is afraid to eat because previous physicians have told him he must not on the basis of a positive skin test. Similarly, the RAST is almost invariably negative when both clinical history and prick test are negative. The authors are grateful to Dr. Robert Orange for his criticism of this manuscript and to Dr. Robert Reisman for his suggestions re methods. We are also grateful to the Department of Medical Publications, Hospital for Sick Children, for help in preparing this manuscript.

Chua et al.

J. ALLERGY CLIN. IMMUNOL. OCTOBER 7976

REFERENCES 1 Collins-Williams, C.: Gastrointestinal allergy in infancy, J. Pediatr. 45: 337, 3954. allergy in infancy and childhood, in Harms, E., 2 Collins-Williams, C. : Gastrointestinal Somatic and psychiatric aspects of childhood allergies, Almsford, N. Y., 1963, editor: Pergamon Press. 3 Shiner, M., Ballard, J., and Smith, M. E.: The small-intestinal mucosa in cow’s milk allergy, Lancet 1: 136, 1975. 4 Rowe, A. H.: Elimination diets and the patient’s allergies, a handbook of allergy, ed. 2, Philadelphia, 1944, Lea & Febiger. 5 Feingold, B. F.: Recognition of food additives as a cause of symptoms of allergy, Ann. Allergy 26: 309, 1968. 6 Chua, Y. Y., Bremner, K., Lakdamalla, N., Llobet, J. L., Kokubu, H. L., Orange, R., and Collins-Williams, C. : In vivo and in vitro correlates of food allergy, J. ALLERGY CLIX. IMMUNOL. 58: 299, 1976. 7 Wide, L.: Clinical significance of measurements of reaginic (IgE) antibody by EAST, Clin. Allergy 3: 583, 1973. 8 Wide, L., Bennich, H., and Johansson, S. G. 0.: Diagnosis of allergy by an in-vitro test for allergen antibodies, Lancet 2: 1105, 1967. assay of allergens, J. 9 Ceska, M., Eriksson, R., and Varga, J. K.: Radioimmunosorbent ALLERGY CLIN. IMMUNOL. 49: 1, 1972. 10 Ceska, M., and Lundkvist, U.: A new and simple radioimmunoassay method for the determination of IgE, Immunochemistry 9: 1021, 1972. 11 Lowry, 0. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J.: Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193: 265, 1951. 12 Aas, K., and Johansson, 8. G. 0.: The radioallergosorbent test in the in vitro diagnosis of multiple reaginio allergy. A comparison of diagnostic approaches, J. ALLERGY CLIN. IMMUXOL. 48: 134, 1971. 13 Aas, K., and Lundkvist, U.: The radioallergosorbent test with a purified allergen from codfish, Clin. Allergy 3: 255, 1973. 14 Hogarth-Scott, R. S., McNicol, R. N., Williams, H. E., and Johansson, S. G. 0.: Diagnosis of allergy in vitro. A comparison between skin sensitivity testing and serum levels of specific IgE antibody in children, Med. J. Aust. 1: 1293, 1973. 15 Foucard, T., Aas, K., and Johansson, S. G. 0.: Concentration of IgE antibodies, P-K titers, and chopped lung titers in sera from children with hypersensitivity to cod, J. ALLERGY CLIN. IMMUWOL. 51: 39, 1973. 16 Hoffman, D. R., and Haddad, Z. H.: Diagnosis of IgE-mediated reactions to food antigens by radioimmunoassay,J. ALLERGY CLIN. IMMUNOL. 54: 165,1974. 17 Sehur, S., Hyde, J. S., and Wypych, J. I.: Egg white sensitivity and atopic eczema, J. ALLERGY CLIN. IMMUNOL. 54: 174, 1974.

Diagnosis of food allergy by the radioallergosorbent test.

iagnosis of food allergy by the radioallergosorbent test Y. Y. Chua, M.D., K. Bremner, BSc., J. 1. Llobet, M.D., H. 1. Kokubu, and C. Collins-Williams...
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