This practice parameter includes an algorithm for the management of stinging insect reactions accompanied by annotations (numbered to correspond to the algorithms). Guideline recommendations are presented in the form of summary statements. After each statement is a letter in parentheses that indicates the strength of the recommendation. Categories of evidence (Ia, Ib, IIa, IIb, III, IV, LB) and strength of recommendations (A-F) are defined at the end of the "Major Recommendations" field.
Box 1: Patient presents with a history of insect sting reaction
Although insects sting many persons each year, most individuals do not have significant reactions and do not need medical attention. Most who are stung have only local reactions and require only symptomatic, if any, treatment. Persons who have a history of insect stings causing systemic reactions require evaluation and usually treatment. Reactions can range from large local swelling to life-threatening systemic reactions. Delayed or toxic reactions might also occur. Taking a careful history can usually make the diagnosis of insect sting reaction.
Box 2: History and physical examination
Identification of the insect responsible might be helpful in diagnosis and treatment. Patients should be encouraged to bring the offending insect, if available, to the physician for identification. Factors that might be helpful in identification include the following:
- The patient's activity at the time of the sting (e.g., cutting a hedge)
- The location of the person at the time of the sting (e.g., close to an insect nest)
- The type of insect activity in the area where the patient was stung
- Visual identification of the insect
Young children present special problems with identification of the culprit insect. The presence of a stinger, which is left primarily by honeybees, or the presence of a pustule as a result of a fire ant sting (up to 24 hours later) might help in insect identification.
Box 3: Was there a systemic reaction?
Most insect stings result in local reactions. These include the following:
- Redness
- Swelling
- Itching and pain
Large local reactions usually include the following features:
- Increase in size for 24 to 48 hours
- Swelling to more than 10 cm in diameter
- Possible involvement of more than one joint area
- 5 to 10 days to resolve
Systemic reactions include a spectrum of manifestations ranging from mild to life-threatening. These include the following:
- Cutaneous responses (e.g., urticaria and angioedema)
- Bronchospasm
- Large airway obstruction (tongue or throat swelling, laryngeal edema)
- Hypotension and shock
The key feature that distinguishes a systemic reaction from a large local reaction is the nature of the systemic symptoms and involvement of parts of the body not contiguous with the site of the sting.
Box 4, A and B: Provide symptomatic treatment if needed
Most insect stings cause local reactions that are of little serious medical consequence, and no specific treatment is usually required. Some local reactions are manifested by extensive erythematous swelling surrounding the sting site that might persist for several days or more and can be accompanied by itching, pain, or both. Cold compresses might help to reduce local pain and swelling. Oral antihistamines and oral analgesics might also help to reduce the pain or itching associated with cutaneous reactions. Many physicians use oral corticosteroids for large local reactions; several reports support their effectiveness, although definitive proof of efficacy through controlled studies is lacking. Because the swelling is caused by mediator release and not by infection, antibiotics are not indicated unless there is evidence of secondary infection (a common misdiagnosis).
Large local reactions can be immunoglobulin E (IgE) mediated but are almost always self-limited and rarely create serious health problems. Patients who have previously experienced large local reactions often have large local reactions to subsequent stings, and up to 10% might eventually have a systemic reaction. Some patients who have had large local reactions might seek guidance on insect avoidance measures. It is optional but usually not necessary to prescribe an injectable epinephrine kit for use if the patient experiences a systemic reaction in the future. The vast majority of patients with large local reactions need only symptomatic care and are not candidates for testing for venom-specific IgE or venom immunotherapy (VIT). Immunotherapy has, however, been shown to reduce the severity of large local reactions with future stings in a patient with a history of severe local reactions and venom-specific IgE, but a previous report found immunotherapy to be ineffective in preventing reoccurrence of large local reactions.
Box 5: Prescribe epinephrine for self-administration/refer to an allergist-immunologist/recommend insect avoidance
Preventive management includes measures to prevent subsequent stings and to prevent subsequent systemic reactions if the patient is stung. Injectable epinephrine should be provided, and the patient should be instructed on its proper administration and use. Patients should also consider obtaining a medical identification bracelet or necklace. A patient with a history of severe reaction should have injectable epinephrine prescribed because even if the test result for venom-specific IgE is negative, there is a small risk of a systemic reaction. For those patients with very mild or questionable systemic reactions and negative test results for venom-specific IgE, there is no consensus regarding prescription of injectable epinephrine because many physicians believe it is not warranted, whereas others prefer to prescribe it in this situation. Referral to an allergist is appropriate for any patient who has had an allergic reaction and is indicated for any patient who is a potential candidate for immunotherapy, as outlined in Box 6.
Box 6, A, B, and C: Is the patient a child whose reaction was limited to the cutaneous system?
The usual criteria for immunotherapy include a systemic reaction to an insect sting and demonstration of venom-specific IgE by either skin or in vitro testing. However, immunotherapy is usually not prescribed for patients 16 years of age and younger who have experienced only cutaneous systemic reactions after an insect sting. They only have about a 10% chance of having a systemic reaction if re-stung, and if a subsequent systemic reaction does occur in these children, it is very unlikely to be worse than the initial isolated cutaneous reaction. Therefore VIT is generally not necessary for patients 16 years of age and younger who have experienced only cutaneous systemic reactions. VIT is still an acceptable option if there are special circumstances, such as lifestyle considerations, that place the child at risk for frequent or multiple stings or if the parents or guardians request venom immunotherapy. Although there is still some controversy in regard to adults who have experienced only cutaneous systemic reactions, there is insufficient evidence to justify withholding VIT for that group of individuals at this time. Although most physicians generally apply the same criteria in selecting patients to receive immunotherapy for fire ant allergy, it is not established that children with only systemic cutaneous reactions are not at risk for serious systemic reactions to subsequent stings. Because the natural history of fire ant hypersensitivity in children who have only cutaneous manifestations has not been well elucidated and there is increased risk of fire ant stings in children who live in areas in which fire ants are prevalent, immunotherapy can be considered for such children.
Box 7: Perform skin testing
Skin tests should be performed on patients for whom venom immunotherapy might be indicated. Skin prick tests with a concentration in the range of 1.0 micrograms/mL are often performed before intracutaneous tests but are not used by all allergists.
Intracutaneous tests usually start with a concentration in the range of 0.001 to 0.01 micrograms/mL. If intracutaneous test results at this concentration are negative, the concentration is increased by 10-fold increments until a positive skin test response occurs or a maximum concentration of 1.0 micrograms/mL is reached. Increasing concentrations of fire ant extract are also used (see text section on fire ants in original guideline document). Positive and negative controls should be placed during skin testing. Because the insect that caused the sting reaction often cannot be identified, testing is usually done with all of the commercially available venom extracts. However, fire ant is only included under special circumstances (see text in original guideline document). Venoms might contain shared antigenic components. Cross-sensitization and extensive immunologic cross-reactivity have been demonstrated between hornet and yellow jacket venoms (vespids); cross-reactivity is also fairly common, although less extensive, between wasp and other venoms and is uncommon between honeybee and vespid venoms. Fire ant venom has very limited cross-reactivity with other stinging insect venoms.
Box 8: Positive skin test response?
Venom immunotherapy is recommended for patients who have had a systemic insect sting reaction, who have a positive skin test response, and who meet the criteria outlined in the annotation for Box 6. There is no absolute correlation between the skin test reactivity or the level of venom-specific IgE and the severity of the reaction to a sting. Near-fatal and fatal reactions have occurred in patients with barely detectable venom IgE antibodies by means of skin or in vitro testing.
Box 8A: Is further testing needed?
Although skin testing has generally been the most reliable diagnostic method used to identify venom-specific IgE and remains the preferred testing modality for most patients, it has been recognized that rare patients might have venom-specific IgE, which is not detected by means of skin testing. Therefore it is recommended that further evaluation for detection of venom-specific IgE be performed if the skin test result is negative in a patient with a history of a severe systemic reaction. There is no clear scientific evidence that defines the severity of a reaction requiring further evaluation for venom-specific IgE. Patients with a history of wheezing with dyspnea or increased respiratory effort, stridor, or other signs of large airway obstruction; hypotension; shock; or loss of consciousness usually need further evaluation.
Box 8, B, C, and D
For patients who have had a severe systemic reaction, as described in the preceding annotation, to an insect sting and who have negative venom skin test responses, it would be prudent to verify this result with repeat skin testing or in vitro testing before concluding that VIT is not necessary. If such test responses are positive, VIT is indicated. If repeat test responses fail to demonstrate the presence of IgE antibodies, there is no indication for venom immunotherapy.
Box 9: Recommend and give VIT
VIT greatly reduces the risk of systemic reactions in stinging insect-sensitive patients with an efficacy of 95 to 97%. Patients who have had a systemic reaction from an insect sting and evidence of venom-specific IgE should therefore be advised to receive VIT. The goal of VIT is primarily to prevent life-threatening reactions. A secondary benefit is that it might alleviate anxiety related to insect stings.
Candidates for VIT should be informed in writing or verbally with documentation in the record about the potential benefits and risks related to the procedure. Patients should receive a description of the procedure and be informed that, although the risk of anaphylaxis is small, they must wait for 20 to 30 minutes after each injection and follow any other specific policies and rules of the provider of the VIT.
In the opinion of some experts, all venoms eliciting positive responses for venom-specific IgE should be included in the immunotherapy vaccine, whereas others contend that if the insect that caused the reaction can be clearly identified, only that venom is needed for VIT, even if skin or in vitro test responses for other stinging insects are positive. Depending on the culprit insect, it is likely that other positive skin test or in vitro test responses will be obtained. Immunotherapy for patients with fire ant hypersensitivity consists of injections with a whole-body vaccine and should be initiated in patients with a history of a systemic reaction to a fire ant sting who have a positive skin test response with whole-body vaccine or a positive in vitro assay result.
VIT injections are generally administered at weekly intervals, beginning with doses no greater than 0.1 to 0.5 micrograms and increasing to a maintenance dose of up to 100 micrograms per venom. The dosage schedule for fire ant immunotherapy is less well defined in terms of starting dose and rapidity of buildup. Although most experts recommend a maintenance dose of 0.5 mL of a 1:100 wt/vol dilution, and there is increasing evidence that this dose is protective, a 1:10 wt/vol maintenance concentration has been recommended by some. The interval between maintenance dose injections can be increased to 4-week intervals during the first year of VIT and eventually to every 6 to 8 weeks during subsequent years. Rapid desensitization protocols have been used successfully and safely to treat flying Hymenoptera and fire ant sting allergy.
Patients with insect sting allergy who are taking beta-adrenergic blocking agents are at greater risk for more serious anaphylaxis to VIT or a sting. Therefore patients who have stinging insect hypersensitivity should not be prescribed beta-adrenergic blocking agents unless absolutely necessary. If the patient who has stinging insect hypersensitivity cannot discontinue the beta-adrenergic blocking agent, the decision to administer immunotherapy should be made on an individual basis after analysis of potential risks and benefits. There are some reports that taking angiotensin-converting enzyme inhibitors might also increase risk.
Box 10 and 10A: Immunotherapy failure
VIT at an accepted maintenance dosage is very effective but does not protect all patients. For patients who have allergic reactions to insect stings while receiving maintenance immunotherapy, it is first necessary to identify the culprit insect. If the insect is the same as that causing the initial reaction, an increase in venom dose of up to 200 micrograms per injection might provide protection.
Box 11: Consider stopping VIT after 3 to 5 years
Guidelines for discontinuation of VIT are evolving. Whereas the package insert for the venom extract product recommends that VIT be continued indefinitely, a decrease in serum venom-specific IgE to insignificant levels or conversion to a negative skin test response have been used as criteria for discontinuing treatment. An increasing body of evidence suggests that despite the persistence of a positive skin test response, approximately 90% of patients will not have a systemic reaction to an insect sting if VIT is stopped after 3 to 5 years, and it is therefore reasonable to consider discontinuation in most patients after therapy of this duration or after losing skin test reactivity. However, there remains a small risk that future sting reactions could occur. In addition, severe reactions have occurred several years after stopping VIT in a small number of patients whose skin test responses became negative while receiving venom immunotherapy. Conversely, although some patients will lose their skin reactivity to stinging insect venom, the persistence of such reactivity does not mean that all such patients are at increased risk of having a systemic reaction if subsequently stung. A decision about the duration of VIT is made individually after discussion between the patient and physician and might involve consideration of lifestyle, occupation, coexistent disease, medications, severity of sting reactions, and other factors. Patients with a history of severe anaphylaxis (shock or loss of consciousness), even after 5 years of immunotherapy, still might be at continued risk for a systemic reaction if VIT is stopped. For this reason, some recommend that immunotherapy be continued indefinitely in such patients (see text in original guideline document for details).
The optimal duration of imported fire ant immunotherapy has not been clearly established. Skin reactivity appears to be a poor indicator of the risk for a systemic reaction to fire ant venom after fire ant immunotherapy. As a result, there is a great deal of variation in recommendations regarding the duration of immunotherapy for fire ant allergy, with some allergists recommending indefinite treatment. Most allergists recommend stopping immunotherapy after a specific period (usually 4 to 5 years), either empirically or when skin test responses become negative. Until further data are available, a definitive recommendation about the duration of immunotherapy for fire ants cannot be made.
Summary Statements
Summary Statement 1
Individuals with a history of a systemic reaction to an insect sting are at increased risk for subsequent systemic sting reactions. This risk can be significantly reduced with VIT. (A)
Summary Statement 2
Individuals who have a history of systemic reactions to insect stings should:
- Be educated in ways to avoid insect stings (D)
- Carry epinephrine for emergency self-treatment (D)
- Undergo specific IgE testing for stinging insect sensitivity and be considered for immunotherapy (testing is optional for those patients who would not be candidates for immunotherapy if test responses were positive) (A)
- Consider obtaining a medical identification bracelet or necklace (D)
Summary Statement 3
Immediate hypersensitivity skin tests with stinging insect venoms are indicated for individuals who are candidates for VIT. (A)
Skin tests, rather than in vitro assays, should be used for initial measurement of venom-specific IgE, except in special circumstances. If skin test responses are negative and the patient has had a severe allergic reaction, further testing (in vitro testing, repeat skin testing, or both) is recommended. (C)
Summary Statement 4
VIT is recommended for all patients who have experienced a systemic reaction to an insect sting and who have specific IgE to venom allergens, with the following special considerations:
- VIT is generally not necessary in children 16 years of age and younger who have experienced cutaneous systemic reactions without other systemic manifestations of a reaction after an insect sting from a wasp, hornet, yellow jacket, or bee. C
- Adults who have experienced only cutaneous manifestations to an insect sting are generally considered candidates for VIT, although the need for immunotherapy in this group of patients is controversial. D
- Because the natural history of fire ant hypersensitivity in children who have only cutaneous manifestations has not been well elucidated and there is increased risk of fire ant stings in children who live in areas where fire ants are prevalent, immunotherapy might be considered for such children. D
Summary Statement 5
Once begun, VIT should usually be continued for at least 3 to 5 years. Although most patients can then safely discontinue immunotherapy, some patients might need to continue immunotherapy indefinitely. C
Definitions:
Strength of Recommendations
- Directly based on category I evidence
- Directly based on category II evidence or extrapolated from category I evidence
- Directly based on category III evidence or extrapolated from category I or II evidence
- Directly based on category IV evidence or extrapolated from category I, II, or III evidence
- Directly based on category LB evidence
- Based on consensus of the Joint Task Force on Practice Parameters
Category of Evidence
Ia Evidence from meta-analysis of randomized controlled trials
Ib Evidence from at least 1 randomized controlled trial
IIa Evidence from at least 1 controlled study without randomization
IIb Evidence from at least 1 other type of quasi-experimental study
III Evidence from nonexperimental descriptive studies, such as comparative studies, correlation studies, and case control studies
IV Evidence from expert committee reports or opinions or clinical experience of respected authorities, or both
LB Evidence from laboratory-based studies
