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Beta-adrenergic blockers, immunotherapy, and skin testing
Position
statement
Beta-adrenergic blockers, and skin testing Although life-threatening reactions are rare, lifethreatening systemic reactions (anaphylaxis and/ or asthmaj and, m some cases, fatalities after injection of allergen extracts have been reported.’ Allergen immunotherapy is a widely accepted and effective option to treat allergic patients and is generally safe when it is performed by knowledgeable physicians.’ Case reports, however, have suggested that a systemic rcaction to allergen extracts, as well as to drugs, foods, insect stings, testing material, and other agents, may occur with greater frequency and be more difficult to treat in patients receiving B-blocking agents. ‘~’’ Beta blockade enhances pulmonary, cardiovascular, and dermatologic end organ effects of mediators and increases mortality associated with experimental anaphylaxis induced by either immunologic or noninmunologic mechanisms.“, ” It has also been suggested that atopic patients may be at special risk for such reactions. Ih. ” The potential for severe bronchospaam in patients receiving B-blocking agents is documented. “-“’ There was no significant increased risk of a systemic reaction to conventional radiocontrast media in patients undergoing cardiac angiography who were receiving B-blocking agents in the only published prospective study addressing this issue. Reactions were mild and responded to therapy, including epinephrine.‘! However, similar studies have not been done to determine the risk with allergen immunotherapy. Although B-blocking agents may delay recovery and make treatment more difficult in some patients. the degree to which these drugs actually increase the incidence of 4uch reactions remains unclear. Nevertheless. there is sufficient medical evidence to adopt a cautious attttude toward the concomitant use of allergen immunotherapy and B-blocking agents and skin testing patients receiving B-blocking agents. In fact, a warning about the concomitant use of B-blocking agents and allergen immunotherapy has been placed in the package insert of allergen extracts. The American Academy of Allergy and Immunology therefore recommends 1. Physicians should be aware of the potential increased risk associated with concomitant administration of allergen immunotherapy and B-
immunotherapy,
2.
3.
4.
5.
6.
7.
blocking agents and should not, when this is possible, use these drugs and immunotherapy concomitantly. When it is possible, an equally effective and safe medication should be substituted for a B-blocking agent if the physician who prescribes or administers immunotherapy is aware that the patient is receiving such a drug. Allergen immunotherapy should be initiated only after weighing the possible benefits and risks in patients who cannot stop B-adrenergic blocking agents. Systemic reactions to skin testing are rare. Nevertheless, special precautions, when these are appropriate, should be taken when the patient who needs sensitivity testing for IgE-mediated disease cannot stop treatment with a B-blocking agent. A warning of the potential dangers of systemic reactions from allergens to which the individual is sensitized should be included in the labeling of Bblocking agents. Physicians and other medical personnel preparing allergen extracts should consider placing a warning label about the risk of concurrent B-blocking agents and allergen immunotherapy on vials dispensed. Prospective studies are necessary to clarify the magnitude of the risk of systemic reactions to allergens in patients who are receiving concomitant therapy with B-blockers.
REFERENCES 1. Lackey RF, Benedict LM. Turkeltaub PC. Bukantz SC. Fatalities from immunotherapy (IT) and akin teatin: (ST). I ALLFKGYCIJN IMMUNOL 1987;79:660. 2. Hepner M. Ownby D. MacKechnie H, Row M. Anderson J. The safety of immunotherapy-a prospective study (AbGrdct]. J AI.L.HKX CLIN IMMUNOL 1987;79: 133. 3. Frankish C. McCourtie II. Toogood JH. Anaphylactic death in patient on beta blockers [Abstract!. Clin Invest Med 1985:X:A42. 4. MadowJitz IS. Schweiger MJ. Severe anaphylactoid reaction to radiographic contrast media: recurrences despite premedicatlon with diphenhydramrne and predniconc. IAMA 1979: 241(16):2813-S. 5. Newman BR. Schultz LK. Epinephrmc-reststant anaphylaxia m a patient taking propranolol hydrochloride. Ann Allergy 1981.17:35.
129
130
Executive
Committee
J. ALLERGY
6. JacobsRL, Rake GW Jr, Fournier DC, et al. Potentiatedanaphylaxis in patients with drug-inducedbeta-adrenergicblockade. J ALLERGYCLIN IMMUNOL1981;68:12.5. 7. Hannaway PJ, Hopper GDK. Severe anaphylaxis and drnginduced beta-blockade. N Engl J Med 1983;308:1536. 8. Bickell WH, Dice WH. Military antishocktrousersin a patient with adrenergic resistant anaphylaxis. Ann Emerg Med 1984;13:189. 9. Awai LW, Mekori YA. Insect sting anaphylaxis and beta adrenergic blockade: a relative contraindication. Ann Allergy 1984;53:48. 10. Ingal M, Goldman G, Page LB. P-blockade in stinging anaphylaxis. JAMA 1984;251:1432. 11. Hamilton G. Severeadversereactionsto urography in patients taking P-adrenergic blocking agents. Can Med Assoc J 1985;133:122. 12. Berkelman RL, Finton RJ, Elsea WR. Beta-adrenergicantagonists and fatal anaphylactic reactions to oral penicillin. Ann Intern Med 1986;104:134. 13. Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. J ALLERGYCLM IMMUNOL1986;78:76. 14. ToogoodJH. Beta-blocker therapy and the risk of anaphylaxis. Can Med Assoc J 1987;136:929. 15. Toogood JH. Risk of anaphylaxis in patients receiving betablockerdrngs[Editorial] .JALLERGYCLINIMMUNOL 1988;81:1. 16. LemanskeRF, CasaleTB , Kaliner M. The autonomicnervous system in allergic disease. In: Kaplan AP, ed. Allergy. New York: Churchill Livingstone, 1985:199-213. 17. Kaliner M, ShelhamerJH, David PB, et al. Autonomic nervous system abnormalities and allergy. Ann Intern Med 1982; 96:349.
Bound volumes
available
18. Zaid G, Beall GN. Bronchial response to beta-adrenergic blockade. N Engl J Med 1966;275:580. 19. Fraley DS, Bruns FJ, Segel DP, Adler S. Propranolol-related bronchospasmin patientswithout history of asthma.SouthMed J 1980;73:238. 20. SchoeneRB, Martin TR, Charan NB, French CL. Timololinduced bronchospasmin asthmatic bronchitis. JAMA 1981; 245:1460. 21. Greenberger PA, Meyers SN, Kramer BL. Effects of betaadrenergiccalcium antagonistson the developmentof anaphylactoid reactionsfrom radiographic contrast media during cardiac angiography. J ALLERGYCLIN IMMUNOL1987;80:698.
American
Academy
Executive Committee of Allergy and Immunology Allen P. Kaplan, John A. Anderson, Martin D. Valentine, Richard F. Lackey, William E. Pierson,
MD MD MD MD MD
Burton Zweiman, Michael A. Kaliner, Lawrence M. Lichtenstein, Philip L. Lieberman,
MD MD MD MD
Guy A. Settipane, MD Albert L. Shefleer, MD John W. Yunginger, MD
to subscribers
Bound volumes of THEJOURNALOFALLERGY ANDCLINICALIMMUNOLOGY are available to subscribers (only) for the 1989 issues from the Publisher, at a cost of $43.00 ($54.50 international) for Vol. 83 (January-June) and Vol. 84 (July-December). Shipping charges are included. Each bound volume contains a subject and author index, and all advertising is removed. Copies are shipped within 30 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C.V. Mosby Co., Circulation Department, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318; phone (800) 3254177,
CLIN. IMMUNOL. JULY 1989
ext. 351.
Subscriptions must be in rbrce to qualify. Bound volumes are not available in place of a regular journal subscription.
statement
Beta-adrenergic blockers, and skin testing Although life-threatening reactions are rare, lifethreatening systemic reactions (anaphylaxis and/ or asthmaj and, m some cases, fatalities after injection of allergen extracts have been reported.’ Allergen immunotherapy is a widely accepted and effective option to treat allergic patients and is generally safe when it is performed by knowledgeable physicians.’ Case reports, however, have suggested that a systemic rcaction to allergen extracts, as well as to drugs, foods, insect stings, testing material, and other agents, may occur with greater frequency and be more difficult to treat in patients receiving B-blocking agents. ‘~’’ Beta blockade enhances pulmonary, cardiovascular, and dermatologic end organ effects of mediators and increases mortality associated with experimental anaphylaxis induced by either immunologic or noninmunologic mechanisms.“, ” It has also been suggested that atopic patients may be at special risk for such reactions. Ih. ” The potential for severe bronchospaam in patients receiving B-blocking agents is documented. “-“’ There was no significant increased risk of a systemic reaction to conventional radiocontrast media in patients undergoing cardiac angiography who were receiving B-blocking agents in the only published prospective study addressing this issue. Reactions were mild and responded to therapy, including epinephrine.‘! However, similar studies have not been done to determine the risk with allergen immunotherapy. Although B-blocking agents may delay recovery and make treatment more difficult in some patients. the degree to which these drugs actually increase the incidence of 4uch reactions remains unclear. Nevertheless. there is sufficient medical evidence to adopt a cautious attttude toward the concomitant use of allergen immunotherapy and B-blocking agents and skin testing patients receiving B-blocking agents. In fact, a warning about the concomitant use of B-blocking agents and allergen immunotherapy has been placed in the package insert of allergen extracts. The American Academy of Allergy and Immunology therefore recommends 1. Physicians should be aware of the potential increased risk associated with concomitant administration of allergen immunotherapy and B-
immunotherapy,
2.
3.
4.
5.
6.
7.
blocking agents and should not, when this is possible, use these drugs and immunotherapy concomitantly. When it is possible, an equally effective and safe medication should be substituted for a B-blocking agent if the physician who prescribes or administers immunotherapy is aware that the patient is receiving such a drug. Allergen immunotherapy should be initiated only after weighing the possible benefits and risks in patients who cannot stop B-adrenergic blocking agents. Systemic reactions to skin testing are rare. Nevertheless, special precautions, when these are appropriate, should be taken when the patient who needs sensitivity testing for IgE-mediated disease cannot stop treatment with a B-blocking agent. A warning of the potential dangers of systemic reactions from allergens to which the individual is sensitized should be included in the labeling of Bblocking agents. Physicians and other medical personnel preparing allergen extracts should consider placing a warning label about the risk of concurrent B-blocking agents and allergen immunotherapy on vials dispensed. Prospective studies are necessary to clarify the magnitude of the risk of systemic reactions to allergens in patients who are receiving concomitant therapy with B-blockers.
REFERENCES 1. Lackey RF, Benedict LM. Turkeltaub PC. Bukantz SC. Fatalities from immunotherapy (IT) and akin teatin: (ST). I ALLFKGYCIJN IMMUNOL 1987;79:660. 2. Hepner M. Ownby D. MacKechnie H, Row M. Anderson J. The safety of immunotherapy-a prospective study (AbGrdct]. J AI.L.HKX CLIN IMMUNOL 1987;79: 133. 3. Frankish C. McCourtie II. Toogood JH. Anaphylactic death in patient on beta blockers [Abstract!. Clin Invest Med 1985:X:A42. 4. MadowJitz IS. Schweiger MJ. Severe anaphylactoid reaction to radiographic contrast media: recurrences despite premedicatlon with diphenhydramrne and predniconc. IAMA 1979: 241(16):2813-S. 5. Newman BR. Schultz LK. Epinephrmc-reststant anaphylaxia m a patient taking propranolol hydrochloride. Ann Allergy 1981.17:35.
129
130
Executive
Committee
J. ALLERGY
6. JacobsRL, Rake GW Jr, Fournier DC, et al. Potentiatedanaphylaxis in patients with drug-inducedbeta-adrenergicblockade. J ALLERGYCLIN IMMUNOL1981;68:12.5. 7. Hannaway PJ, Hopper GDK. Severe anaphylaxis and drnginduced beta-blockade. N Engl J Med 1983;308:1536. 8. Bickell WH, Dice WH. Military antishocktrousersin a patient with adrenergic resistant anaphylaxis. Ann Emerg Med 1984;13:189. 9. Awai LW, Mekori YA. Insect sting anaphylaxis and beta adrenergic blockade: a relative contraindication. Ann Allergy 1984;53:48. 10. Ingal M, Goldman G, Page LB. P-blockade in stinging anaphylaxis. JAMA 1984;251:1432. 11. Hamilton G. Severeadversereactionsto urography in patients taking P-adrenergic blocking agents. Can Med Assoc J 1985;133:122. 12. Berkelman RL, Finton RJ, Elsea WR. Beta-adrenergicantagonists and fatal anaphylactic reactions to oral penicillin. Ann Intern Med 1986;104:134. 13. Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. J ALLERGYCLM IMMUNOL1986;78:76. 14. ToogoodJH. Beta-blocker therapy and the risk of anaphylaxis. Can Med Assoc J 1987;136:929. 15. Toogood JH. Risk of anaphylaxis in patients receiving betablockerdrngs[Editorial] .JALLERGYCLINIMMUNOL 1988;81:1. 16. LemanskeRF, CasaleTB , Kaliner M. The autonomicnervous system in allergic disease. In: Kaplan AP, ed. Allergy. New York: Churchill Livingstone, 1985:199-213. 17. Kaliner M, ShelhamerJH, David PB, et al. Autonomic nervous system abnormalities and allergy. Ann Intern Med 1982; 96:349.
Bound volumes
available
18. Zaid G, Beall GN. Bronchial response to beta-adrenergic blockade. N Engl J Med 1966;275:580. 19. Fraley DS, Bruns FJ, Segel DP, Adler S. Propranolol-related bronchospasmin patientswithout history of asthma.SouthMed J 1980;73:238. 20. SchoeneRB, Martin TR, Charan NB, French CL. Timololinduced bronchospasmin asthmatic bronchitis. JAMA 1981; 245:1460. 21. Greenberger PA, Meyers SN, Kramer BL. Effects of betaadrenergiccalcium antagonistson the developmentof anaphylactoid reactionsfrom radiographic contrast media during cardiac angiography. J ALLERGYCLIN IMMUNOL1987;80:698.
American
Academy
Executive Committee of Allergy and Immunology Allen P. Kaplan, John A. Anderson, Martin D. Valentine, Richard F. Lackey, William E. Pierson,
MD MD MD MD MD
Burton Zweiman, Michael A. Kaliner, Lawrence M. Lichtenstein, Philip L. Lieberman,
MD MD MD MD
Guy A. Settipane, MD Albert L. Shefleer, MD John W. Yunginger, MD
to subscribers
Bound volumes of THEJOURNALOFALLERGY ANDCLINICALIMMUNOLOGY are available to subscribers (only) for the 1989 issues from the Publisher, at a cost of $43.00 ($54.50 international) for Vol. 83 (January-June) and Vol. 84 (July-December). Shipping charges are included. Each bound volume contains a subject and author index, and all advertising is removed. Copies are shipped within 30 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C.V. Mosby Co., Circulation Department, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318; phone (800) 3254177,
CLIN. IMMUNOL. JULY 1989
ext. 351.
Subscriptions must be in rbrce to qualify. Bound volumes are not available in place of a regular journal subscription.