Special report
NIH Consensus Development Conference on Emergency Treatment of Insect Sting Allergy The National Institute of Allergy and Infectious Diseases convened an NIH Consensus Development Conference on Emergency Treatment of Insect Sting Allergy at Bethesda on September 14, 1978. This conference was one of a series of consensus development programs initiated by NIH to make useful new knowledge Inore quickly available to practicing physicians. The process brings together authorities in many specialized areas to review recent findings and to reach agreement on the efficacy and safety of diagnostic and treatment approaches. Dr. Phililp M. Gottlieb, Clinical Associate Professor of Medicine, Emeritus, of Temple University School of Medicine in Philadelphia, Pennsylvania, chaired a panel made up of physicians, nurses, emergency technicians, educators, and lawyers. The panel heard invited speakers describe insect behavior, epidemiology, diagnosis and treatment of insect allergy, pharmacology of epinephrine, and the legal aspects of emergency treatment. Brief position papers were presented by representatives from a number of interested national organizations. Excerpts from letters from a number of national, regional, and local allergy societies, sent in response to a request for opinions, were read. The panel then evaluated the availability and effectiveness of treatment presently administered by health care professionals and others. Following are short summaries of the presentations heard by the panel. Behavior
of insects
Dr. Allen W. Benton, Professor of Entomology at Pennsylvania State University, confirmed that most serious allergic reactions in humans are caused by certain kinds of stinging Hymenoptera insects, including bees, wasps, hornets, yellow jackets, and fire ants. Most stinging Hymenoptera can sting repeatedly. Only the honeybee has a barbed stinger that remains in the victim’s skin as the bee flies away and ~--Reprint requests to: NL4ID Information 7A?,7. NIH. Bethesda, MD 20014.
Office,
Bldg.
31, Rm.
dies. The yellow jacket, one of the most vicious stinging insects, is the most common cause of anaphylactic reactions. Dr. Benton commented that many more insects are found in suburban areas than in rural areas because of the greater availability of over-wintering places in the suburbs. Control methods include several effective bee-wasp-hornet sprays currently on the market. He also suggested pouring ammonia on ground nests at night, and then covering the nest. Epidemiology
and treatment
Dr. Robert E. Reisman, Buffalo General Hospital, New York, cited retrospective studies that suggest that 0.4% of the population has anaphylactic reactions due to stinging insects. Most reactions occur in males younger than 20 years of age, although fatalities most often occur in adults older than 40 years. Every year SOto 100 persons in this country are reported to have died from reactions to stings, although the actual number may be even higher. For most individuals there are no criteria to predict occurrence of anaphylaxis. A person’s previous reaction to an insect sting is not a reliable indicator of the severity of future reactions. Finally, Dr. Reisman observed that comparisons of patients with fatal and non-fatal anaphylaxis suggest that epinephrine is the appropriate medical therapy and that the earlier the drug is administered, the better the outcome. Dr. Martin D. Valentine, Associate Professor of Medicine at the Johns Hopkins University School of Medicine, agreed that prompt treatment of generalized sting reactions is essential and that injected epinephrine is the drug and route of choice, He explained that serious, generalized reactions to Hymenoptera stings are mediated by antibodies of the IgE class, and are secondary to sensitization to specific antigens that he believes are found in the venoms of these insects. Immunotherapy can build up protective, or blocking, antibodies of the IgG class. Dr. Valentine believes, on the basis of experimental Vol.
63, No. 2, pp. 77-79
78
NIH Consensus
Development
J. ALLERGY
Conference
studies, that relevant antigens are contained in venom and not in insect bodies. Therefore, he recommended that the materials most suitable for diagnosis and therapy are those that contain the greatest amount of venom protein and the least amount of insect body contaminants. At the present time, honeybee venom is available for testing only. The preparations currently in general use for testing and immunotherapy are whole body extracts of Hymenoptera. Dr. Valentine confirmed Dr. Reisman’s assertion that data do not exist that allow predicting of the risk of anaphylaxis in patients who have positive skin tests but no prior history of reactions. Insect sting kits and epinephrine Mr. M. W. Giboney, President of Hollister-Stier Laboratories in Spokane, Washington, described the emergency treatment kits currently available to allergic persons with a physician’s prescription. Kits are manufactured by two companies, Hollister-Stier Laboratories and Nelco Laboratories, Inc. Each kit contains enough epinephrine for a normal adult dose. The kit also may contain an antihistamine, disinfecting swabs, a tourniquet, and detailed instructions to the patients. Both companies also recommend that the physician carefully explain to the patient how to use the kit. Both kits are compact and designed to be carried by the patient. Dr. Harry Keiser, Clinical Director of the National Heart, Lung, and Blood Institute, discussed the pharmacology of epinephrine, stating that it was clearly the drug of choice in treating any serious systemic allergic reaction. However, it must be administered quickly, since it is less beneficial once a person is in anaphylactic shock. Epinephrine has several safety features, including limiting its own absorption by inducing vasoconstriction. The only major precaution is to be sure that it is not administered intravascularly. Modern preparations remain stable for many years. When decomposition (or inactivation) does occur, the solution turns a distinctive pink-brown color and should be replaced. However, there is no evidence that decomposition makes the solution more toxie. Dr. Claude Frazier, Asheville, North Carolina, proposed that an insect sting kit containing premeasured doses of epinephrine be available to nonphysicians trained to recognize symptoms of systemic reactions to insect stings. He further proposed that such trained non-physicians be authorized to inject pre-measured epinephrine subcutaneously as emergency, on-the-spot treatment of victims of all forms of anaphylaxis, with or without specific authorization of
CLIN. IMMUNOL. FEBRUARY 1979
a physician. He re-emphasized the importance of prompt treatment to stave off potentially fatal anaphylaxis long enough to transport the victim to a physician or hospital for further necessary medical treatment. Legal considerations Dr. Richard A. Nicklas, Bureau of Drugs, Food and Drug Administration, agreed that insect hypersensitivity is a significant medical problem. He recommended that all allergic persons should obtain kits from their physicians and that special individuals should be trained to administer epinephrine under certain circumstances. Dr. Nicklas did not consider it advisable or necessary to make injectable epinephrine available over-the-counter. Mr. Kenneth Wing, School of Law, University of North Carolina, and Dr. George A. Sprecace, an allergist from New London, Connecticut, both commented on the legal aspects. Dr. Sprecace described his long and eventually successful efforts to get specific state laws exempting teachers and other school personnel from liability when they administer emergency treatment to allergic persons. Mr. Wing commented that, at the present time, most state laws probably do not prohibit use of the kit by trained non-medical personnel. These persons would be protected from liability under so-called Good Samaritan laws. An important factor to consider before introducing new legislation is that any law that might be introduced to alter the State Medical Practices Act is likely to meet considerable organized opposition more because it would change existing law than because of the specific issue involved. Panel recommendations After considering all the information presented, the panel made the following recommendations: The panel recognized that everyone is a potential victim of life-threatening or fatal allergic reactions from stinging insects. Although valid data regarding the incidence of these occurrences are not available at this time, the data presented to the panel suggested that such allergic reactions occur with greater frequency than is generally thought. Prior identification of those individuals who will so react is difficult. Better education of the lay and professional populations will improve documentation of these events and tend to promote immediate and effective medical treatment, which can prevent the majority of fatalities. Efforts to reduce the size of the problem require two approaches. The educational approach entails
VOLUME NUMBER
63 2
instructing both laymen and professionals on the dangers of insect stings and on the means of treating them. The service approach entails increasing the availability of treatment, to the maximum extent permitted by law, by allowing and encouraging all personnel who are properly trained to administer such emergency treatment at the site of the emergency. The belief that certain individuals are restricted from providing treatment may be based less on the applicable law than on misunderstanding of the state of law in th!!s area. Given the objective of increasing the availability of emergency treatment, the panel encourages evaluation of the legal risks, placing them in proper perspective. Teaching films and written materials for the lay public should be developed and distributed to help promote recognition of the problem of anaphylactic reactions to insect stings and to make known the available therapeutic regimens. These should be disseminated by interested organizations such as school and parent organizations, youth groups, farmers. industrial and labor organizations, and other groups whose members are at high risk. Persons who have had allergic reactions to insects are urged to identify their sensitivity to others; e.g., they should have such information with them, in writing, at all times. Education of physicians should include information on emergency management of systemic reactions, emergency drugs, and the use of immunotherapy (hyposensitization). Physicians and other health care personnel should instruct patients about the importance of avoiding insect stings and about the treatment of life-threatening reactions to such stings. Warnings
insect sting allergy
79
should be given about the possibility of adverse drug interactions between epinephrine and other drugs. The panel considered and rejected the option of making insect sting treatment kits, containing a predetermined dose of epinephrine for injection, available as an over-the-counter product. In the absence of individualized instruction for its administration, the panel believes there is considerable potential for inappropriate use of the kit by individuals with hypertension, certain cardiovascular diseases. or those who are taking certain medications. The panel believes these concerns would not be addressed adequately by labels or printed instructions that might be required for an over-the-counter item. The drug abuse potential for such kits was also of great concern. Research is needed to determine whether there may be other drugs and/or modes of administration that would be more effective and safer than current methods. Panel members included Dr. Gottlieb, Dr. James Ford, New York, N. Y., Ms. Jessie M. Smallwood, New Orleans, La., Ms. Virginia Rosenbaum, Chevy Chase, Md., Mr. Nathan Hershey, Pittsburgh, Pa., Ms. Carolyn Whitaker, Tompkinsville, Ky., Dr. Francis C. Lowell, Boston, Mass.. Mr. Michael R. Pollard, Washington, D. C., Dr. Robert J. Brennan. Fort Lauderdale, Fla., Dr. Donald E. Cook, Greeley, Colo., Dr. Robert J. Dockhom, Prairie Village, Kan., Dr. William E. Pierson, Seattle, Wash., Dr. J. Warrick Thomas, Richmond, Va., Capt. Mary Beth Michos, Rockville, Md., Dr. William Waddell, Jr., Galax, Va., and Dr. August Watanabe, Indianapolis, Ind.
NIH Consensus Development Conference on Emergency Treatment of Insect Sting Allergy The National Institute of Allergy and Infectious Diseases convened an NIH Consensus Development Conference on Emergency Treatment of Insect Sting Allergy at Bethesda on September 14, 1978. This conference was one of a series of consensus development programs initiated by NIH to make useful new knowledge Inore quickly available to practicing physicians. The process brings together authorities in many specialized areas to review recent findings and to reach agreement on the efficacy and safety of diagnostic and treatment approaches. Dr. Phililp M. Gottlieb, Clinical Associate Professor of Medicine, Emeritus, of Temple University School of Medicine in Philadelphia, Pennsylvania, chaired a panel made up of physicians, nurses, emergency technicians, educators, and lawyers. The panel heard invited speakers describe insect behavior, epidemiology, diagnosis and treatment of insect allergy, pharmacology of epinephrine, and the legal aspects of emergency treatment. Brief position papers were presented by representatives from a number of interested national organizations. Excerpts from letters from a number of national, regional, and local allergy societies, sent in response to a request for opinions, were read. The panel then evaluated the availability and effectiveness of treatment presently administered by health care professionals and others. Following are short summaries of the presentations heard by the panel. Behavior
of insects
Dr. Allen W. Benton, Professor of Entomology at Pennsylvania State University, confirmed that most serious allergic reactions in humans are caused by certain kinds of stinging Hymenoptera insects, including bees, wasps, hornets, yellow jackets, and fire ants. Most stinging Hymenoptera can sting repeatedly. Only the honeybee has a barbed stinger that remains in the victim’s skin as the bee flies away and ~--Reprint requests to: NL4ID Information 7A?,7. NIH. Bethesda, MD 20014.
Office,
Bldg.
31, Rm.
dies. The yellow jacket, one of the most vicious stinging insects, is the most common cause of anaphylactic reactions. Dr. Benton commented that many more insects are found in suburban areas than in rural areas because of the greater availability of over-wintering places in the suburbs. Control methods include several effective bee-wasp-hornet sprays currently on the market. He also suggested pouring ammonia on ground nests at night, and then covering the nest. Epidemiology
and treatment
Dr. Robert E. Reisman, Buffalo General Hospital, New York, cited retrospective studies that suggest that 0.4% of the population has anaphylactic reactions due to stinging insects. Most reactions occur in males younger than 20 years of age, although fatalities most often occur in adults older than 40 years. Every year SOto 100 persons in this country are reported to have died from reactions to stings, although the actual number may be even higher. For most individuals there are no criteria to predict occurrence of anaphylaxis. A person’s previous reaction to an insect sting is not a reliable indicator of the severity of future reactions. Finally, Dr. Reisman observed that comparisons of patients with fatal and non-fatal anaphylaxis suggest that epinephrine is the appropriate medical therapy and that the earlier the drug is administered, the better the outcome. Dr. Martin D. Valentine, Associate Professor of Medicine at the Johns Hopkins University School of Medicine, agreed that prompt treatment of generalized sting reactions is essential and that injected epinephrine is the drug and route of choice, He explained that serious, generalized reactions to Hymenoptera stings are mediated by antibodies of the IgE class, and are secondary to sensitization to specific antigens that he believes are found in the venoms of these insects. Immunotherapy can build up protective, or blocking, antibodies of the IgG class. Dr. Valentine believes, on the basis of experimental Vol.
63, No. 2, pp. 77-79
78
NIH Consensus
Development
J. ALLERGY
Conference
studies, that relevant antigens are contained in venom and not in insect bodies. Therefore, he recommended that the materials most suitable for diagnosis and therapy are those that contain the greatest amount of venom protein and the least amount of insect body contaminants. At the present time, honeybee venom is available for testing only. The preparations currently in general use for testing and immunotherapy are whole body extracts of Hymenoptera. Dr. Valentine confirmed Dr. Reisman’s assertion that data do not exist that allow predicting of the risk of anaphylaxis in patients who have positive skin tests but no prior history of reactions. Insect sting kits and epinephrine Mr. M. W. Giboney, President of Hollister-Stier Laboratories in Spokane, Washington, described the emergency treatment kits currently available to allergic persons with a physician’s prescription. Kits are manufactured by two companies, Hollister-Stier Laboratories and Nelco Laboratories, Inc. Each kit contains enough epinephrine for a normal adult dose. The kit also may contain an antihistamine, disinfecting swabs, a tourniquet, and detailed instructions to the patients. Both companies also recommend that the physician carefully explain to the patient how to use the kit. Both kits are compact and designed to be carried by the patient. Dr. Harry Keiser, Clinical Director of the National Heart, Lung, and Blood Institute, discussed the pharmacology of epinephrine, stating that it was clearly the drug of choice in treating any serious systemic allergic reaction. However, it must be administered quickly, since it is less beneficial once a person is in anaphylactic shock. Epinephrine has several safety features, including limiting its own absorption by inducing vasoconstriction. The only major precaution is to be sure that it is not administered intravascularly. Modern preparations remain stable for many years. When decomposition (or inactivation) does occur, the solution turns a distinctive pink-brown color and should be replaced. However, there is no evidence that decomposition makes the solution more toxie. Dr. Claude Frazier, Asheville, North Carolina, proposed that an insect sting kit containing premeasured doses of epinephrine be available to nonphysicians trained to recognize symptoms of systemic reactions to insect stings. He further proposed that such trained non-physicians be authorized to inject pre-measured epinephrine subcutaneously as emergency, on-the-spot treatment of victims of all forms of anaphylaxis, with or without specific authorization of
CLIN. IMMUNOL. FEBRUARY 1979
a physician. He re-emphasized the importance of prompt treatment to stave off potentially fatal anaphylaxis long enough to transport the victim to a physician or hospital for further necessary medical treatment. Legal considerations Dr. Richard A. Nicklas, Bureau of Drugs, Food and Drug Administration, agreed that insect hypersensitivity is a significant medical problem. He recommended that all allergic persons should obtain kits from their physicians and that special individuals should be trained to administer epinephrine under certain circumstances. Dr. Nicklas did not consider it advisable or necessary to make injectable epinephrine available over-the-counter. Mr. Kenneth Wing, School of Law, University of North Carolina, and Dr. George A. Sprecace, an allergist from New London, Connecticut, both commented on the legal aspects. Dr. Sprecace described his long and eventually successful efforts to get specific state laws exempting teachers and other school personnel from liability when they administer emergency treatment to allergic persons. Mr. Wing commented that, at the present time, most state laws probably do not prohibit use of the kit by trained non-medical personnel. These persons would be protected from liability under so-called Good Samaritan laws. An important factor to consider before introducing new legislation is that any law that might be introduced to alter the State Medical Practices Act is likely to meet considerable organized opposition more because it would change existing law than because of the specific issue involved. Panel recommendations After considering all the information presented, the panel made the following recommendations: The panel recognized that everyone is a potential victim of life-threatening or fatal allergic reactions from stinging insects. Although valid data regarding the incidence of these occurrences are not available at this time, the data presented to the panel suggested that such allergic reactions occur with greater frequency than is generally thought. Prior identification of those individuals who will so react is difficult. Better education of the lay and professional populations will improve documentation of these events and tend to promote immediate and effective medical treatment, which can prevent the majority of fatalities. Efforts to reduce the size of the problem require two approaches. The educational approach entails
VOLUME NUMBER
63 2
instructing both laymen and professionals on the dangers of insect stings and on the means of treating them. The service approach entails increasing the availability of treatment, to the maximum extent permitted by law, by allowing and encouraging all personnel who are properly trained to administer such emergency treatment at the site of the emergency. The belief that certain individuals are restricted from providing treatment may be based less on the applicable law than on misunderstanding of the state of law in th!!s area. Given the objective of increasing the availability of emergency treatment, the panel encourages evaluation of the legal risks, placing them in proper perspective. Teaching films and written materials for the lay public should be developed and distributed to help promote recognition of the problem of anaphylactic reactions to insect stings and to make known the available therapeutic regimens. These should be disseminated by interested organizations such as school and parent organizations, youth groups, farmers. industrial and labor organizations, and other groups whose members are at high risk. Persons who have had allergic reactions to insects are urged to identify their sensitivity to others; e.g., they should have such information with them, in writing, at all times. Education of physicians should include information on emergency management of systemic reactions, emergency drugs, and the use of immunotherapy (hyposensitization). Physicians and other health care personnel should instruct patients about the importance of avoiding insect stings and about the treatment of life-threatening reactions to such stings. Warnings
insect sting allergy
79
should be given about the possibility of adverse drug interactions between epinephrine and other drugs. The panel considered and rejected the option of making insect sting treatment kits, containing a predetermined dose of epinephrine for injection, available as an over-the-counter product. In the absence of individualized instruction for its administration, the panel believes there is considerable potential for inappropriate use of the kit by individuals with hypertension, certain cardiovascular diseases. or those who are taking certain medications. The panel believes these concerns would not be addressed adequately by labels or printed instructions that might be required for an over-the-counter item. The drug abuse potential for such kits was also of great concern. Research is needed to determine whether there may be other drugs and/or modes of administration that would be more effective and safer than current methods. Panel members included Dr. Gottlieb, Dr. James Ford, New York, N. Y., Ms. Jessie M. Smallwood, New Orleans, La., Ms. Virginia Rosenbaum, Chevy Chase, Md., Mr. Nathan Hershey, Pittsburgh, Pa., Ms. Carolyn Whitaker, Tompkinsville, Ky., Dr. Francis C. Lowell, Boston, Mass.. Mr. Michael R. Pollard, Washington, D. C., Dr. Robert J. Brennan. Fort Lauderdale, Fla., Dr. Donald E. Cook, Greeley, Colo., Dr. Robert J. Dockhom, Prairie Village, Kan., Dr. William E. Pierson, Seattle, Wash., Dr. J. Warrick Thomas, Richmond, Va., Capt. Mary Beth Michos, Rockville, Md., Dr. William Waddell, Jr., Galax, Va., and Dr. August Watanabe, Indianapolis, Ind.
