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Skin testing and radioallergosorbent testing (RAST) for diagnosis of specific allergens responsible for IgE-mediated diseases
Position
statement
Skin testing and radioallergosorbent testing (RAST) for diagnosis of specific allergens responsible for IgE-mediated diseases*
This position statement reflects the state of the art at this time. It will be reassessed on a continuing basis as new data are developed. The traditional approach to the specific diagnosis of reaginic (IgE-mediated) allergic disorders has been the use of skin tests of a variety of types. These tests have in common small quantities of allergenic extracts introduced below the epidermis. Within 15 to 20 min. a characteristic wheal-and-flare reaction can be observed in patients who have IgE antibodies that recognize one or more of the test allergens. This bioassay is highly sensitive, cost-effective, and safe when used by experienced personnel with due attention to technique and reasonable precautions. ’ In 1967 Wide et a1.2 first reported from Sweden a solid-phase radioimmunoassay capable of detecting the minute quantities of allergen-specific IgE antibodies that circulate in the serum of allergic patients. Over the last decade, this in vitro test, the RAST, has been refined and developed into a commercially available laboratory test, which is now widely available both in clinical laboratories and in kit form for performance in physicians’ offices. Refinement of methodology, particularly appropriate threshold determination, continues as recently reviewed elsewhere .:( This statement concerns the relative merits of skin tests and RASTs for routine diagnosis of specific allergens responsible for IgE-mediated diseases. By necessity, this is a complex statement because consideration of this subject must deal with the relation of these tests to the broad program for diagnosis and management of allergic diseases, selection and interpretation of the tests, proper performance of the tests, the relative advantages of each test, the relative cost of skin tests and RASTs for the same diagnostic information, and the potential for abuse of both tests. The Executive Committee of The American Acad__*From the Practice Standards of Allergy and Immunology;
Committee. reviewed
The American Academy and revised March 1983.
emy of Allergy and Immunology has taken the position that most physicians agree on certain basic principles with regard to the care of patients with allergic diseases that are outlined in paragraphs A to E.4, ’ A. Patientswith allergic diseases are numerous, sick. need medical care, and of necessity will contract for medical care for these diseases. B. Physicians who provide medical care for patients with allergic diseases should be properly trained, should maintain their training, and should expend considerable skill, effort, and time in order to provide adequate services to allergic patients. They should be compensated fairly for these necessary and properly performed services. Proper management of the allergic patient should include the following: Thorough history, physical examination, and appropriate laboratory procedures including skin tests and, where appropriate, RASTs to identify the factors provoking the allergic and any concomitant diseases are necessary. Training the patient (and his or her family) in procedures for the amelioration and/or elimination of the many factors that provoke allergic diseases that include at least exposure to allergens, tobacco, and other inhaled irritants, emotional tension, infection, climate factors, obesity, and exercise is important. Concomitant diseases such as diabetes and hypertension must be properly controlled, and their management must be put in proper perspective in the patient’s overall program for medical care. Medication for control of symptoms of allergic diseases will frequently be needed despite the care outlined in paragraphs 2, 3, and 5 and will include antihistamines, corticosteroids, bronchodilators, and other drugs. This medication should be carefully supervised and adjusted to the patient’s needs. Appropriate immunotherapy should be given when indicated and should be properly supervised by the allergist either in his or her office or elsewhere. An individualized and often complex program is essential to provide good long-term medical care for the total patient. This will often involve both the patient and his family. It is important to emphasize that such a program demands a broad approach and the use of multiple procedures. Physi515
516
Position statement
cian training programs, physicians providing care. and insurance programs should insist on such an integrated broad approach. C. Private and/or national health insurance should provide proper benefits for the patient with allergic diseases. D. Physicians must guard against the injudicious use of skin tests and RASTh. Indications for testing should be clearly documented in the patient’s record.’ E. The Executive Committee of The American Academy of Allergy and Immunology has expressed concern about the use of the results of allergy skin tests or in vitro assays of specific IgE antibodies as the sole bazis for formulating allergenic extracts for immunotherapy. Such practice has often been conducted by physicians who have not had direct personal contact with the patient and by allergenic extract suppliers. The Executive Committee has stated that it strongly believes that good medical practice is best conducted by physicians. including allergists. who personally perform or supervise the history and physical examination. which are the fundamental investigative procedures, and M ho personally supervise further diagnostic and therapeutic procedures. The validity of laboratory procedures that may be useful in investigating possible allergic disorders. such as allergy akin tests and RASTs. is based not only upon the proper technical performance of these tests but also on their clinical interpretation and on the choice of appropriate tests. The necessity for evaluating the results of such tests within the context of the detailed historic information and the patient’s physical status cannot be overemphasized. Consequently. the indirect or remote direction of allergy investigation or therapy of the type described in paragraph E, is not in the interest of good patient care and should be strongly discouraged.” F. With reference to the comparative merits of skin tests and RASTs for routine diagnosis of specific allergens responsible for IgE-mediated disease, the following statements are considered to be basically correct at this time: 1. Optimally performed skin tests and RASTs both detect IgE antibody accurately and reproducibly.“, ‘. ’ 2. Within the constraints of each method, both skin tests and RASTs yield information of a semiquantitative nature. but RASTs are less sensitive than skin tests.” 3. Results of both tests usually correlate equally well with allergic symptoms and signs produced by exposure to the specific allergen tested.“. ‘. ’ 4. Both tests can be used as grounds for instituting immunotherapy in an efficient and economic manner. Where RAST is used as grounds for immunotherapy. a skin test with the planned initial dilution of immunotherapy solution should be done before starting immunotherapy to prove that the patient tolerates in vivo administration of this allergenic extract..‘. 7 5. Skin tests appear to be superior to currently available
J ALLERGY CLIN. IMMUNOL NOVEMBER 1983
RASTs in the diagnosis of certain life-threatening anaphylactic states in which maximum sensitivity is important. particularly in the diagnosis of penicillin and Hymenoptera allergy.” 6. The results of skin tests are more immediately available. Where both tests can be initiated at the time of the patient’s visit. the results of skin tests are available in about 45 min; those of RASTs are available in 2 to 3 days.’ 7. RAST is preferable to skin testing in certain conditions where skin testing is unsatisfactory. particularly where there is dermatographia or widespread skin disease.’ G. Skin tests are usually more cost effective than RAST\. Based on skin test and RAST charges from sources participating in the analysis, RASTs cost from two to six times more than skin tests per allergen tested.!’ H. Abuse of skin testing and RAST is of great concern to allergy patients, practitioners. and insurance companies. Some recognized abuses are listed below: I. Commercial availability of extracts of substances that are not proved allergens and use of these for skin tests and RASTs.” Some commercial laboratories have marketed RASTs for substances not proved to be allergenic. such as aspirin. radiocontrast dyes. and codeine. Such tests can be highly misleading and a source of unnecessary expense. 2. Poor quality control of potentially proper skin tehts and RASTs in physicians’ offices’! This abuse is often caused by poorly trained or inexperienced personnel. 3. Poor quality control of RAST and use of unorthodox procedures exist in some commercial laboratories.” 4. Irresponsible promotional techniques may be used: a. By commercial firms who sell equipment for RAST testing in physicians’ offices by emphasizing the profit motive rather than the cost/benefit ratio of skin testing and RAST b. By individual physicians who misrepresent the value of skin testing and RAST and urge patients to accept tests in inappropriate clinical circumstances (e.g.. RAST for patients already shown to have negative reactions to appropriate and more sensitive skin tests). 5. Inappropriate selection and interpretation of skin tests and RASTs with reference to the results of history and physical examination”: This abuse often takes the form of using routinely a large battery of tests that include tests for many allergens that are not present in the home, work area. or geographic locality of the patient and tests that experienced allergists would consider irrelevant and a source of needless expense. I. Abuses can be minimized by the following measures: 1. Increasing regulatory control over allergenic extracts used for skin tests and RASTs so that extracts are not licensed for sale unless proved to be effective for diagnosis and of specified potency: The Executive
VOLUME 72 NUMBEE 5,PART
Position statement
1
Committee of The American Academy of Allergy and Immunology has recommended that preparation. determination of biologic potency, labeling. storage. dilution. and shipment of allergenic extracts conform to currently acceptable standards that will ensure acceptable potency when the extract is used. I” 2. The Federal Government Center for Disease Control. the Health and Human Services Department. and some professional medical organizations have programs for monitoring quality control in a number of clinical pathology laboratories. The Executive Committee of the American Academy of Allergy and Immunology has recommended that similar monitoring of tests for specific IgE (such as RAST) done in commercial laboratories be encouraged.” 3. Physicians and patients must be informed and trained with reference to proper procedures and quality controls for skin testing and RAST and with reference to costs and realistic benefits to be expected from each.‘. Ii 4. Rational and consistent policies of insurance carriers with regard to reimbursement for diagnostic tests used for the evaluation of patients with allergic diseases that encourage the use of the most cost-effective procedures are to be established. For instance, consider reimbursement ceilings or “caps” applicable to both skin tests and RASTs to discourage abuse, provide incentive for the more cost-effective procedure when possible, and assure fairness to patients suffering from allergic diseases.
517
REFERENCES 1.
2. 3.
Norman PS: In ~~ivomethods of study of allergy. rn Middleton E, Reed CE. Ellis EF, editors: Allergy: principle and practice. vol. 1. St. Louis, 1978, The C. V. Mosby Co.. p. 256. Wide L. Bennich H. Johansson SGO: Diagnosis of allergy by an in \?tro test for allergen antibodies. Lancet 2: 1105. 1967. Adkinson NF Jr: The radioallergosorbent test in 198 I - limitations and refinements. J ALI.ERGY CI.I~ IWWNOI~ 67: 87. 1981.
4.
Statement by American Academy of Allergy to American Medical Association Council on Medical Services, Feb. 26,
5.
Statement by the Executive Committee of the American Academy of Allergy. J ALLERGY CLIN IMMLNOI. 62:71, 1978. Adkinson NF Jr: The radioallergosorbent test: use and abuses. J ALLERGY CLIN IMMUNOL 65:l. 1980. Santrach PJ, Parker JL, Jones RT. Yunginger JW: Diagnostic and therapeutic applications of a moditied radioallergosorbent test and comparison with the conventional radioallergosorbent test. J AI.I.ERCY CI.IN IMMUNOL 67:97. 1981. The American Academy of Allergy and Immunology: Statement by the Executive Committee. Position statement on use of radioallergosorbent and IgE tests in practice. J At LERGY
1977.
6. I.
8.
CLIN
IMMUNOL
66:431.
1980.
9.
E&ins RE 111.Tang DB. London0 S. et al: Variability in the measurement of specific IgE antibody by the RAST procedure.
10.
The American Academy of Allergy and Immunology: Statement by the Executive Committee. Position statement on allergen standardization. J AI.LERGY CLIN IMMUNOL 66:431.
J ALLERGY
1980.
CLIN
IMMUNOL
69245.
1982.
statement
Skin testing and radioallergosorbent testing (RAST) for diagnosis of specific allergens responsible for IgE-mediated diseases*
This position statement reflects the state of the art at this time. It will be reassessed on a continuing basis as new data are developed. The traditional approach to the specific diagnosis of reaginic (IgE-mediated) allergic disorders has been the use of skin tests of a variety of types. These tests have in common small quantities of allergenic extracts introduced below the epidermis. Within 15 to 20 min. a characteristic wheal-and-flare reaction can be observed in patients who have IgE antibodies that recognize one or more of the test allergens. This bioassay is highly sensitive, cost-effective, and safe when used by experienced personnel with due attention to technique and reasonable precautions. ’ In 1967 Wide et a1.2 first reported from Sweden a solid-phase radioimmunoassay capable of detecting the minute quantities of allergen-specific IgE antibodies that circulate in the serum of allergic patients. Over the last decade, this in vitro test, the RAST, has been refined and developed into a commercially available laboratory test, which is now widely available both in clinical laboratories and in kit form for performance in physicians’ offices. Refinement of methodology, particularly appropriate threshold determination, continues as recently reviewed elsewhere .:( This statement concerns the relative merits of skin tests and RASTs for routine diagnosis of specific allergens responsible for IgE-mediated diseases. By necessity, this is a complex statement because consideration of this subject must deal with the relation of these tests to the broad program for diagnosis and management of allergic diseases, selection and interpretation of the tests, proper performance of the tests, the relative advantages of each test, the relative cost of skin tests and RASTs for the same diagnostic information, and the potential for abuse of both tests. The Executive Committee of The American Acad__*From the Practice Standards of Allergy and Immunology;
Committee. reviewed
The American Academy and revised March 1983.
emy of Allergy and Immunology has taken the position that most physicians agree on certain basic principles with regard to the care of patients with allergic diseases that are outlined in paragraphs A to E.4, ’ A. Patientswith allergic diseases are numerous, sick. need medical care, and of necessity will contract for medical care for these diseases. B. Physicians who provide medical care for patients with allergic diseases should be properly trained, should maintain their training, and should expend considerable skill, effort, and time in order to provide adequate services to allergic patients. They should be compensated fairly for these necessary and properly performed services. Proper management of the allergic patient should include the following: Thorough history, physical examination, and appropriate laboratory procedures including skin tests and, where appropriate, RASTs to identify the factors provoking the allergic and any concomitant diseases are necessary. Training the patient (and his or her family) in procedures for the amelioration and/or elimination of the many factors that provoke allergic diseases that include at least exposure to allergens, tobacco, and other inhaled irritants, emotional tension, infection, climate factors, obesity, and exercise is important. Concomitant diseases such as diabetes and hypertension must be properly controlled, and their management must be put in proper perspective in the patient’s overall program for medical care. Medication for control of symptoms of allergic diseases will frequently be needed despite the care outlined in paragraphs 2, 3, and 5 and will include antihistamines, corticosteroids, bronchodilators, and other drugs. This medication should be carefully supervised and adjusted to the patient’s needs. Appropriate immunotherapy should be given when indicated and should be properly supervised by the allergist either in his or her office or elsewhere. An individualized and often complex program is essential to provide good long-term medical care for the total patient. This will often involve both the patient and his family. It is important to emphasize that such a program demands a broad approach and the use of multiple procedures. Physi515
516
Position statement
cian training programs, physicians providing care. and insurance programs should insist on such an integrated broad approach. C. Private and/or national health insurance should provide proper benefits for the patient with allergic diseases. D. Physicians must guard against the injudicious use of skin tests and RASTh. Indications for testing should be clearly documented in the patient’s record.’ E. The Executive Committee of The American Academy of Allergy and Immunology has expressed concern about the use of the results of allergy skin tests or in vitro assays of specific IgE antibodies as the sole bazis for formulating allergenic extracts for immunotherapy. Such practice has often been conducted by physicians who have not had direct personal contact with the patient and by allergenic extract suppliers. The Executive Committee has stated that it strongly believes that good medical practice is best conducted by physicians. including allergists. who personally perform or supervise the history and physical examination. which are the fundamental investigative procedures, and M ho personally supervise further diagnostic and therapeutic procedures. The validity of laboratory procedures that may be useful in investigating possible allergic disorders. such as allergy akin tests and RASTs. is based not only upon the proper technical performance of these tests but also on their clinical interpretation and on the choice of appropriate tests. The necessity for evaluating the results of such tests within the context of the detailed historic information and the patient’s physical status cannot be overemphasized. Consequently. the indirect or remote direction of allergy investigation or therapy of the type described in paragraph E, is not in the interest of good patient care and should be strongly discouraged.” F. With reference to the comparative merits of skin tests and RASTs for routine diagnosis of specific allergens responsible for IgE-mediated disease, the following statements are considered to be basically correct at this time: 1. Optimally performed skin tests and RASTs both detect IgE antibody accurately and reproducibly.“, ‘. ’ 2. Within the constraints of each method, both skin tests and RASTs yield information of a semiquantitative nature. but RASTs are less sensitive than skin tests.” 3. Results of both tests usually correlate equally well with allergic symptoms and signs produced by exposure to the specific allergen tested.“. ‘. ’ 4. Both tests can be used as grounds for instituting immunotherapy in an efficient and economic manner. Where RAST is used as grounds for immunotherapy. a skin test with the planned initial dilution of immunotherapy solution should be done before starting immunotherapy to prove that the patient tolerates in vivo administration of this allergenic extract..‘. 7 5. Skin tests appear to be superior to currently available
J ALLERGY CLIN. IMMUNOL NOVEMBER 1983
RASTs in the diagnosis of certain life-threatening anaphylactic states in which maximum sensitivity is important. particularly in the diagnosis of penicillin and Hymenoptera allergy.” 6. The results of skin tests are more immediately available. Where both tests can be initiated at the time of the patient’s visit. the results of skin tests are available in about 45 min; those of RASTs are available in 2 to 3 days.’ 7. RAST is preferable to skin testing in certain conditions where skin testing is unsatisfactory. particularly where there is dermatographia or widespread skin disease.’ G. Skin tests are usually more cost effective than RAST\. Based on skin test and RAST charges from sources participating in the analysis, RASTs cost from two to six times more than skin tests per allergen tested.!’ H. Abuse of skin testing and RAST is of great concern to allergy patients, practitioners. and insurance companies. Some recognized abuses are listed below: I. Commercial availability of extracts of substances that are not proved allergens and use of these for skin tests and RASTs.” Some commercial laboratories have marketed RASTs for substances not proved to be allergenic. such as aspirin. radiocontrast dyes. and codeine. Such tests can be highly misleading and a source of unnecessary expense. 2. Poor quality control of potentially proper skin tehts and RASTs in physicians’ offices’! This abuse is often caused by poorly trained or inexperienced personnel. 3. Poor quality control of RAST and use of unorthodox procedures exist in some commercial laboratories.” 4. Irresponsible promotional techniques may be used: a. By commercial firms who sell equipment for RAST testing in physicians’ offices by emphasizing the profit motive rather than the cost/benefit ratio of skin testing and RAST b. By individual physicians who misrepresent the value of skin testing and RAST and urge patients to accept tests in inappropriate clinical circumstances (e.g.. RAST for patients already shown to have negative reactions to appropriate and more sensitive skin tests). 5. Inappropriate selection and interpretation of skin tests and RASTs with reference to the results of history and physical examination”: This abuse often takes the form of using routinely a large battery of tests that include tests for many allergens that are not present in the home, work area. or geographic locality of the patient and tests that experienced allergists would consider irrelevant and a source of needless expense. I. Abuses can be minimized by the following measures: 1. Increasing regulatory control over allergenic extracts used for skin tests and RASTs so that extracts are not licensed for sale unless proved to be effective for diagnosis and of specified potency: The Executive
VOLUME 72 NUMBEE 5,PART
Position statement
1
Committee of The American Academy of Allergy and Immunology has recommended that preparation. determination of biologic potency, labeling. storage. dilution. and shipment of allergenic extracts conform to currently acceptable standards that will ensure acceptable potency when the extract is used. I” 2. The Federal Government Center for Disease Control. the Health and Human Services Department. and some professional medical organizations have programs for monitoring quality control in a number of clinical pathology laboratories. The Executive Committee of the American Academy of Allergy and Immunology has recommended that similar monitoring of tests for specific IgE (such as RAST) done in commercial laboratories be encouraged.” 3. Physicians and patients must be informed and trained with reference to proper procedures and quality controls for skin testing and RAST and with reference to costs and realistic benefits to be expected from each.‘. Ii 4. Rational and consistent policies of insurance carriers with regard to reimbursement for diagnostic tests used for the evaluation of patients with allergic diseases that encourage the use of the most cost-effective procedures are to be established. For instance, consider reimbursement ceilings or “caps” applicable to both skin tests and RASTs to discourage abuse, provide incentive for the more cost-effective procedure when possible, and assure fairness to patients suffering from allergic diseases.
517
REFERENCES 1.
2. 3.
Norman PS: In ~~ivomethods of study of allergy. rn Middleton E, Reed CE. Ellis EF, editors: Allergy: principle and practice. vol. 1. St. Louis, 1978, The C. V. Mosby Co.. p. 256. Wide L. Bennich H. Johansson SGO: Diagnosis of allergy by an in \?tro test for allergen antibodies. Lancet 2: 1105. 1967. Adkinson NF Jr: The radioallergosorbent test in 198 I - limitations and refinements. J ALI.ERGY CI.I~ IWWNOI~ 67: 87. 1981.
4.
Statement by American Academy of Allergy to American Medical Association Council on Medical Services, Feb. 26,
5.
Statement by the Executive Committee of the American Academy of Allergy. J ALLERGY CLIN IMMLNOI. 62:71, 1978. Adkinson NF Jr: The radioallergosorbent test: use and abuses. J ALLERGY CLIN IMMUNOL 65:l. 1980. Santrach PJ, Parker JL, Jones RT. Yunginger JW: Diagnostic and therapeutic applications of a moditied radioallergosorbent test and comparison with the conventional radioallergosorbent test. J AI.I.ERCY CI.IN IMMUNOL 67:97. 1981. The American Academy of Allergy and Immunology: Statement by the Executive Committee. Position statement on use of radioallergosorbent and IgE tests in practice. J At LERGY
1977.
6. I.
8.
CLIN
IMMUNOL
66:431.
1980.
9.
E&ins RE 111.Tang DB. London0 S. et al: Variability in the measurement of specific IgE antibody by the RAST procedure.
10.
The American Academy of Allergy and Immunology: Statement by the Executive Committee. Position statement on allergen standardization. J AI.LERGY CLIN IMMUNOL 66:431.
J ALLERGY
1980.
CLIN
IMMUNOL
69245.
1982.