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27 Allergy to Insect Stings By SusanWaserman, MD, FRCP; and Abdullah Aburiziza, MD, XXX S tinging insects which cause IgE-mediated reactions belong to the order Hymenoptera. There are four families within that order, and including ent Vespidae (yellow jackets, hornets and paper wasps), Apidae (bees), Halic- pla cem tidae (sweatbees) and Formicidae (ants). Two families, the Vespidae and the fo rJu s t Apidae are associated with most stinging insect allergy. Hymenoptera venom anaphylaxis has been associated with about 40 deaths per year in the U.S., yellow jackets the most common cause in North America.1 Asymptomatic venom sensitization is common in adults but transient, and can disappear at a rate of 12% per year.2 Fatalities are less common in children than adults.3 Approximately one half of fatal reactions occur in individuals with no previous history of allergic re- actions to stings.4 Though patients with atopy have an increased risk of be- coming sensitized, they do not seem to develop systemic reactions more Dr. Waserman is an Associate frequently than non atopics.5 Professor of Medicine and the This article reviews the clinical features of stinging-insect allergy, as well as Training Program Director for diagnosis and treatment, including avoidance, injectable epinephrine, and Allergy and Clinical Immunology venom immunotherapy. at McMaster University, Hamilton, Ontario. Classification of Reactions Reactions from insect stings are classified as local (normal or large local) or sys- temic (allergic and non-allergic). Local reactions are limited to the area con- tiguous with the sting site. Large local reactions are also contiguous but are Dr. Aburiziza is an defined as being 10 cm in diameter or larger and lasting longer than 24 hours.6 xxxxxxxxxxxxxxxxxxxxxxxxxxxxx Frequently, these are misdiagnosed as cellulitis and treated with antibiotics. xxxxxxxxxxxxxxxxxxxxxxxxxxxxx Local reactions are not IgE-mediated, hence venom skin testing and im- xxxxxxxxxxxxxxxxxxxxxxxxxxxxx munotherapy are not indicated, however large locals may be and should be evaluated by an allergist. Systemic allergic reactions occur at sites distant to the sting and affect 0.4% to 0.8% of children and 3% of adults.1 These are IgE-mediated. Symptoms range from mild (cutaneous manifestations) to severe, with symptoms such as laryngeal edema, bronchospasm, and hypotension. Non-allergic systemic re- actions are less common and are not IgE-mediated. These include nephrotic syndrome, serum sickness, neurologic manifestations (Guillain Barre), rhab- domyolysis, and hemolysis.7 Allergy&Asthma
28 Allergy to Insect StingsA positive skin or RAST (radioallergosorbent A positive skin or radioallergosorbent test (RAST), a blood test which measures IgE to each oftest), a blood test which measures IgE to each the venoms, in conjunction with a systemic reac-of the venoms, in conjunction with a systemic tion is diagnostic of venom allergy. In the weeks after a sting reaction, some patients have negativereaction is diagnostic of venom allergy. skin tests attributable to a refractory period. They should have repeat skin testing after four to six Diagnosis weeks. Patients with a negative skin test and a his- Recognition of anaphylaxis is often difficult, es- tory of anaphylaxis should have a RAST. If results pecially with the first sting and if urticaria are ab- are still negative, skin tests should be repeated sent. Vasovagal responses may be confused with after three to six months.8 anaphylaxis, however these are usually accompa- nied by bradycardia and anaphylaxis with com- Treatment pensatory tachycardia. An elevated serum Acute Therapy. Avoidance of stinging insects is tryptase, a mast-cell-specific enzyme, provides ad- important. Patients are advised to destroy nests, ditional evidence for anaphylaxis, but it is not wear shoes, avoid perfumes outdoors, cover very sensitive. garbage receptacles and use insecticides. Treat- Insect identification is also difficult, however ment of local reactions includes icing, elevation, certain factors may be helpful. Honeybees leave a analgesics, and antihistamines. stinger behind, whereas vespids do not. Yellow For acute systemic reactions, epinephrine jackets tend to be aggressive, and will sting if un- 1:1,000 solution, given as 0.01 ml/kg (maximum provoked. They are found around food and dose 0.3 ml/kg) is injected intramuscularly. All pa- garbage cans. Since they nest in the ground peo- tients with insect-sting anaphylaxis should carry ple are often stung while mowing the lawn. Hor- an epinephrine autoinjector, prescribed according nets are also aggressive and are found in nests, to weight. A “junior” dose of 0.15 mg of epi- trees and shrubs. nephrine is for patients weighing 15 kg to 30 kg Skin testing to the five Hymenoptera standard- and the regular dose of 0.30 mg of epinephrine is ized venoms is the standard method of diagnosis. for patients weighing greater than 30 kg. Patients Skin-prick tests to venoms, if negative, are fol- should be taught to self inject if necessary after a sting. The dose can be repeated in five to 10 min- utes if symptoms persist and patients should beSystemic allergic reactions occur at sites distant instructed to call 911. An antihistamine can beto the sting and affect 0.4% to 0.8% of chil- given, but is second-line therapy, and its use should not delay the administration of epineph-dren and 3% of adults.1 rine. Corticosteroids have no proven benefit in the acute period but may be useful in treating the lowed by intradermal skin tests. Intradermal con- late-phase manifestations of anaphylaxis. centrations start at 0.001 µg/ml to 0.01 µg/ml and Referral to an allergist is extremely important increase 10 fold to a maximum of 1 µg/ml. Skin for diagnostic skin testing, patient education, and tests are indicated when immunotherapy is being venom immunotherapy. considered, namely for individuals who have had Immunotherapy. Venom-specific immunother- a systemic allergic reaction. For children aged two apy is the treatment of choice for stinging-insect to 16 years who have had only cutaneous reac- allergy. It is safe and highly effective for prevent- tions, immunotherapy is not given since most ing future reactions. Immunotherapy is 97% to (90%) will not experience more severe or progres- 100% effective in preventing systemic reac- sive symptoms with their next sting (Table 1). tions,9whereas reactions in untreated individuals Allergy&Asthma
29 Table 1 Selection of Patients for Immunotherapy Reaction to sting Result of skin test or RAST Venom immunotherapy? Child Systemic, non-life-threatening, immediate, generalized urticaria, angiodema, erythema, pruritus + or − No Systemic, life-threatening, possible cutaneous symptoms, but also respiratory symptoms (laryngeal edema or bronchospasm) or cardiovascular symptoms (hypotension, shock) + Yes Adult Systemic + Yes Systemic − No Child/Adult Large local (> 2 inches, > 24 hour duration) + or − No Normal (< 2 inches, < 24 hour duration) + or − Nois as high as 60%. temic reaction. About 3% to 12% of patients The venoms used for immunotherapy are the have treatment-induced systemic reactions thatsame as those used for skin testing (honeybee, yel- generally are mild and occur in the early phases oflow jacket, yellow hornet, white-faced hornet, immunotherapy. If a systemic reaction occurs,wasp, and fire ant, if applicable). The routine reg- one half of the dose is given the next week. Thisimen begins with an injection of 0.01 µg and ad- approach, however, is individualized to the pa-vances weekly to 100 µg (equivalent to twostings). The maintenance dose of 100 µg is given Avoidance of stinging insects is important.every four weeks for a year, and then every six toeight weeks. Venom selection is based mainly on Patients are advised to destroy nests, wear shoes,skin-test results, clinical history and a pattern of avoid perfumes outdoors, cover garbagevenom cross-reactivity. One recommendation isthat immunotherapy includes all venoms giving a receptacles and use insecticides.positive skin test. However there is allergeniccross-reactivity of the four vespid venoms, hence tient. Pretreatment with antihistamines weremost patients with multiple sensitivities can be found to be effective in reducing immunother-protected by immunotherapy with yellow jacket apy reactions. Large local reactions occur invenom alone.10 25% of children and 50% of adults, usually at Venom immunotherapy is well tolerated. Most higher doses. Although troublesome, they dopatients receive their injections in an allergist’s of- not predict an increased risk of future systemicfice until the maintenance dose is reached. Pa- reactions to treatment.tients should remain for 30 minutes after each No long-term side effects have been associatedinjection in a setting equipped to handle a sys- with venom immunotherapy thus far. It is safe Allergy&Asthma
30 Allergy to Insect StingsReferral to an allergist is extremely important for leisure activities, medications, and coexistent dis- eases should be considered); the conversion to adiagnostic skin testing, patient education, and negative skin test is one criterion for stoppingvenom immunotherapy. venom immunotherapy. For most patients, it is time-based and discontinued after five years, after which protection is long-lasting in most, even if during pregnancy, with no increased risk of mis- the skin test remains positive. For those who had carriage or congenital anomalies, and it does not a severe initial allergic reaction, a decision to con- result in allergic sensitization in the child. tinue for longer or indefinitely may be made. Recommendations regarding discontinuation of venom immunotherapy include the following Conclusion from the American Academy of Allergy Asthma Venom allergy is one of the most common causes and Immunology: The decision to stop should be of anaphylaxis. All patients with a systemic aller- made after thorough discussion by the physician gic reaction should be evaluated by an allergist for and patient (patient variables such as vocation, consideration of immunotherapy. References: study of the natural history of large local reactions after Hy- 1. Golden DB, Marsh DG, Kagey-Sobotka A, et al. Epidemiology of menoptera stings in children. J Pediatr 1984; 104:664–8. Insect Allergy. JAMA 1989; 262: 240-4. 7. Light WC, Reisman RE, Shimizu M, et al. Unusual reactions fol- 2. Golden D, Marsh D, Freidhoff L, et al. Natural history of Hy- lowing insect stings: clinical features and immunologic analysis. J menoptera venom sensitivity in adults. J Allergy Clin Immunol Allergy Clin Immunol 1977; 59:391–7. 1997: 100:760-6 8. Selcow J, Mendelson L, Rosen J: Anaphylactic reactions in skin 3. Deaths from each cause by 5-year age groups, race, and sex: test-negative patients. J Allergy Clin Immunol 1980; 67:400. United States, 1980–1999. Hyattsville (MD): National Center 9. Hunt KJ, Valentine MD, Sobotka AK, et al. A controlled trial of for Health Statistics. immunotherapy in insect hypersensitivity. N Engl J Med 1978; 4. Barnard JH. Studies of 400 Hymenoptera sting deaths in the 299:157. United States. J Allergy Clin Immunol 1973; 52:259–64. 10. Reisman RE, Livingston A. Venom immunotherapy: 10 years of 5. Birnbaum J,Vervloet D, Charpin D. Atopy and systemic reactions to experience with administration of single venoms and 50 micro- hymenoptera stings. Allergy Proc 1994; 15(2):49-52. grams maintenance dose. J Allergy Clin Immunol 1992; 89:1189– 6. Graft DF, Schuberth KC, Kagey-Sobotka A, et al. A prospective 95. Allergy&Asthma