INTRODUCTION — Hymenoptera species that sting humans include bees, wasps, yellow jackets, hornets, and imported fire ants. Most people develop only minor local reactions, but patients with venom allergy are at risk for systemic allergic reactions (ie, anaphylaxis), which can be particularly severe and are a leading cause of anaphylaxis fatalities. There are also several uncommon and delayed types of reactions that may develop after Hymenoptera stings, such as serum sickness.
This topic reviews the types of reactions that result from Hymenoptera stings, including local reactions and systemic allergic reactions, and the acute management of each. The diagnosis and long-term management of Hymenoptera allergy are presented separately. (See "Diagnosis of Hymenoptera venom allergy" and "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action".)
OVERVIEW — The insects that are responsible for the majority of serious sting-related reactions belong to the order Hymenoptera. The
Stinging Hymenoptera — Hymenoptera families of medical interest include the following [1-3]:
The winged Hymenoptera:
●Apidae family (honey bees (picture 1) and bumble bees).
●Vespidae family (yellow jackets (picture 2), yellow hornets, white-faced hornets, and paper wasps (picture 3)).
The wingless Hymenoptera:
●Formicidae family (fire ants (picture 4), harvester ants, bulldog ants, and jack jumper ants). The clinical manifestations and treatment of fire ant stings are discussed in detail separately. (See "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment".)
Hymenoptera generally sting people in self-defense or to protect their nests or hives. Their stings are acutely painful, and patients are aware that a sting has occurred, although they may not have visualized the insect. Identification of the responsible winged Hymenoptera species can be difficult since the resultant lesions are similar in appearance. A culprit species can sometimes be identified based upon nest location and appearance, geographic location, or setting in which the sting occurred. (See "Stinging insects: Biology and identification".)
Insect and stinger removal — Bees (and occasionally yellow jackets) have a barbed stinging apparatus that becomes lodged in the skin and rips away, along with the venom sac, from the insect's body following a sting event. The venom is released within the first several seconds after the sting [4], so if the insect or stinger can be flicked off of the skin immediately, it may help limit the amount of venom injected. However, if the patient presents minutes later, immediate stinger removal is not critical, because the venom will have already been fully expelled. Remaining stingers should eventually be removed because they can occasionally cause foreign body reactions [5,6].
Imported fire ants grasp the skin firmly with their mandibles and inflict multiple stings per insect, so these should be promptly removed as well.
LOCAL REACTIONS — Local reactions consist of symptoms that are confined to the tissues contiguous with the sting site. They are usually mild and transient, although some patients develop large local reactions (LLRs) or (rarely) secondary bacterial infections.
Uncomplicated local reactions — A typical local reaction to a Hymenoptera sting is redness and an area of painful swelling (1 to 5 cm) at the site of the sting that develops within minutes and resolves within a few hours (picture 5). Occasionally, swelling may last one to two days. Uncomplicated local reactions may be treated with cold compresses.
Imported fire ant stings typically cause pustule-like lesions at the site of the sting(s) within about 24 hours (picture 6) [7]. These pseudopustules are sterile, and patients should be advised not to open them, as this can lead to infection. In the absence of this advice, patients tend to unroof the lesions, either because of the intense pruritus associated with fire ant stings or because conventional wisdom dictates "draining the infection" [8]. Additional measures for the care of local reactions to fire ant stings are presented elsewhere. (See "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment".)
Large local reactions — Approximately 10 percent of individuals develop exaggerated redness and swelling at the site of the sting that gradually enlarges over one to two days (picture 7). This response is called a large local reaction (LLR). LLRs peak at approximately 48 hours and then gradually resolve over 5 to 10 days. The area of swelling typically measures about 10 cm in diameter [9,10].
Treatment — Treatment of LLRs is based upon symptoms. We know of no published studies comparing different treatments. Our approach is described below:
●Cold compresses are soothing acutely. The limb should be elevated if the sting is on an extremity.
●Oral prednisone 40 to 60 mg given as a single dose or rapidly tapered over two to five days may help reduce significant swelling.
●If the reaction is painful, nonsteroidal antiinflammatory drugs (NSAIDs) can be helpful.
●Pruritus can be treated with oral antihistamines (eg, cetirizine, 10 mg once daily) and high-potency topical corticosteroids (eg, fluocinonide 0.05% or clobetasol 0.05% ointment, applied every four hours) until the itching subsides.
Hymenoptera stings are considered "clean" for the purposes of tetanus vaccination. Stings are very superficial, and there are no published reports of tetanus infection following Hymenoptera stings. A tetanus booster is not necessary following a sting unless there was a concomitant soil-contaminated injury. (See "Tetanus-diphtheria toxoid vaccination in adults", section on 'Immunization for patients with injuries'.)
Excluding a secondary bacterial infection — Most Hymenoptera stings do not become superinfected, although this can occur. An infected sting must be differentiated from an LLR. (See 'Large local reactions' above.)
Infection is suspected when redness, swelling, and pain become dramatically worse three to five days after the sting, when the typical LLR is beginning to regress. The presence of fever suggests infection, but lymphangitis streaks may be seen with either infection or an uncomplicated LLR. If the clinician is unsure, a course of oral antibiotics may be prudent. (See "Acute cellulitis and erysipelas in adults: Treatment".)
The stings of yellow jackets and imported fire ants are more likely to become infected than those of other species [11]. Yellow jackets tend to scavenge around rotting food and presumably carry bacteria on their exterior. Fire ant stings cause sterile pustule-like lesions that can become infected if opened.
Future risk of systemic reactions — Patients with a history of an LLR most often have the same response to subsequent stings [12,13]. It is not known if the risk of recurrent LLRs changes over time or is influenced by the frequency of stings.
The risk for a systemic allergic reaction after an LLR has been estimated at approximately 7 percent (4 to 10 percent), based on observational studies [14]. However, the risk of moderate or severe anaphylaxis is lower and estimated at <3 percent. Most of the subsequent reactions that are more severe than LLRs are still limited to the skin (generalized urticaria and angioedema) and are called cutaneous systemic reactions. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Patients with past cutaneous systemic reactions'.)
However, a 2019 prospective study of over 600 patients with an LLR from three European countries found a significantly higher rate of systemic reactions (16 percent) among the 225 patients who reported subsequent stings, including 11 percent that were serious [15]. In this population, a positive intradermal skin test at a low venom concentration (0.001 ug/L) correlated with a higher risk of subsequent systemic reaction. Because these findings are so different from the existing understanding of the natural history of LLRs, both the investigators and the author and editor of this topic emphasize the need for replication in other populations and study designs before changing practice.
Until more data are available, we suggest that patients with a history of an LLR, similar to those with cutaneous systemic reactions, be advised that the chance of future anaphylaxis is relatively low and that current guidelines do not require epinephrine autoinjectors or VIT. However, the guidelines also provide that patients who are uncomfortable with the uncertainty surrounding future risk of a systemic reaction or who have other risk factors may be offered an epinephrine autoinjector prescription and referred to an allergist for further discussion. Note that there is some evidence that being told to carry an epinephrine autoinjector is associated with a decrease in quality of life, so the decision must be individualized [16].
Pathogenesis — LLRs are believed to be immunoglobulin E (IgE)-mediated based upon the following evidence:
●The frequency of positive venom skin tests or venom-specific serum IgE is the same in patients with LLRs as in those with anaphylactic reactions [12].
●In one patient, large local reactivity to fire ant stings was transferred passively (using the Prausnitz-Kustner reaction) [17]. Also in this report, eosinophils, which are found in the late phase of IgE-mediated allergic reactions, were demonstrated in biopsy specimens from patients with fire ant-induced LLRs but not in specimens from patients without LLRs.
●Both sting-induced anaphylaxis and LLRs can be treated with venom immunotherapy, a technique classically applied to IgE-mediated reactions. Although most patients with LLRs are not treated with venom immunotherapy, treatment can be considered for those wishing to lower the risk of future anaphylaxis further or who have frequent stings and wish to take measures to reduce the severity of future LLRs (and the need for glucocorticoid treatment). The indications for venom immunotherapy are reviewed in more detail separately. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action".)
The reason that patients with past LLRs are at low risk for future anaphylaxis while those with past systemic allergic reactions are at high risk, when both reactions appear to be IgE-mediated, is unknown.
Prevention — Some individuals develop predictable LLRs with every Hymenoptera sting and seek advice on how to prevent this. Our clinical experience is that administration of a single dose of 20 to 60 mg of prednisone (depending upon the historical severity of the LLR) within two hours of the sting often attenuates the response.
SYSTEMIC ALLERGIC REACTIONS/ANAPHYLAXIS — The most dangerous immediate reaction to Hymenoptera stings is a systemic allergic reaction, or anaphylaxis (the terms are used interchangeably in this review). Anaphylaxis may be defined as a serious allergic reaction that is rapid in onset and may cause death [18]. Venom-induced anaphylaxis involves signs and symptoms in one or more anatomic systems distant from the site of the sting.
A single sting is sufficient to precipitate a severe reaction in a venom-allergic individual, and insect stings are a leading cause of fatal anaphylaxis [19]. Venom-induced anaphylaxis can be particularly severe, sometimes persisting despite multiple doses of epinephrine [20,21].
Epidemiology of venom anaphylaxis — Anaphylaxis is reported in 0.3 to 3 percent of stings [18,22,23], affecting up to 8 percent of some populations [24,25]. Hymenoptera stings cause at least 40 identified deaths annually in the United States, and reported rates are similar in other parts of the world [24,26,27]. The true incidence of fatal reactions may be higher because sudden deaths occurring outdoors may be mistakenly attributed to heart attacks or strokes. One study found a high frequency of venom-specific immunoglobulin E (IgE) in the postmortem serum of individuals who had died suddenly of unknown cause [28]. Even more suspicious is the presence of both elevated serum tryptase (a mediator that is released from mast cells and basophils during anaphylaxis) and venom IgE in deaths of unknown cause [29]. The utility of tryptase measurements in the postmortem diagnosis of anaphylaxis is reviewed elsewhere. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)
An American survey study of the general population found that approximately 3 percent of people reported experiencing some systemic symptom after a Hymenoptera sting [30]. Since approximately 60 to 90 percent of patients with a suggestive clinical history have venom-specific IgE upon evaluation, an estimated 2 percent of the adult population (and 0.5 percent of children) could have venom allergy.
About one-half of patients who die as a result of Hymenoptera-induced anaphylaxis did not know that they had an allergy [24,31]. In the survey mentioned previously, the majority of patients who reported past systemic symptoms had not sought medical attention. Thus, venom allergy is very likely under-recognized and underdiagnosed.
Venom allergy can develop at any age, but adults suffer more severe reactions, and most deaths occur in this age group. Men are affected more often than women, probably due to a greater prevalence of outdoor occupations [19,31]. Not surprisingly, beekeepers are at highest risk [32].
Patients with concomitant cardiovascular disease and a poor tolerance for biochemical and physiologic stress are at particular risk for severe and fatal anaphylaxis [33-35]. (See "Fatal anaphylaxis".)
One to 2 percent of patients with severe anaphylactic reactions following Hymenoptera stings are subsequently found to have clonal mast cell disease (eg, cutaneous and systemic mastocytosis, as well as other clonal mast cell disorders) [36-38]. These patients may have a characteristic dermatitis called urticaria pigmentosa (picture 8) or report a history of multiple allergic reactions to various triggers. (See "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis", section on 'Allergic disorders' and "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Introduction'.)
Signs and symptoms — When evaluating a patient with any symptoms of an allergic reaction, it is important to ask specifically about the different manifestations of anaphylaxis, as patients often focus on just one symptom and do not recognize other symptoms or may not report sensations with which they are unfamiliar and cannot readily describe. Sudden illness on the golf course or while working in the yard may be readily mistaken for a cardiovascular event or asthma attack, unless the patient is carefully questioned/examined to reveal the full array of signs and symptoms [29].
There are over 40 signs and symptoms of anaphylaxis (table 1). In venom-induced anaphylaxis, the following are regularly reported:
●Skin symptoms, such as generalized urticaria, flushing, and angioedema, are common. This is the sole manifestation of a systemic allergic reaction in the majority of children (ie, about 60 percent). In contrast, only about 15 percent of adults with systemic reactions develop isolated cutaneous symptoms [39].
●Respiratory symptoms include hoarse voice or upper airway obstruction due to edema of the pharynx and epiglottis and shortness of breath and wheezing due to bronchoconstriction.
●Cardiovascular symptoms, ranging from lightheadedness to hypotension, shock, and circulatory collapse, are features of severe sting anaphylaxis [27,31,40].
Adults tend to have more severe systemic reactions, and the vast majority of deaths occur in adults as a result of circulatory collapse. Ninety percent of adults have reactions involving the respiratory or cardiovascular system, whereas only 30 percent of reactions in children demonstrate cardiopulmonary symptoms [21]. In adults, the absence of cutaneous manifestations is associated with more severe reactions [40].
Most episodes of venom anaphylaxis develop rapidly, and the precipitous appearance of symptoms is a feature of severe reactions. One study in adults identified the onset of symptoms within five minutes of the sting as a feature of severe anaphylaxis [40]. Typically, symptoms initially escalate and then resolve in a uniphasic manner. However, a small percentage follows a biphasic course, in which the initial reaction is treated and resolves or resolves spontaneously, but there is a recurrence of symptoms hours later [24]. Protracted anaphylaxis is another uncommon presentation [39]. The clinical manifestations and temporal patterns of anaphylaxis from all causes are reviewed separately. (See "Anaphylaxis: Emergency treatment".)
Diagnosis and laboratory findings — The diagnosis of anaphylaxis is clinical and based upon signs and symptoms in the setting of a suggestive history. Three diagnostic criteria have been proposed, each reflecting a different clinical presentation of anaphylaxis (table 2) [18]. Anaphylaxis is highly likely when any one criterion is fulfilled. The diagnosis can be particularly challenging when cardiovascular signs and symptoms exist in isolation (eg, criterion 3). (See "Anaphylaxis: Emergency treatment".)
The diagnosis of anaphylaxis can be further supported by the documentation of elevated concentrations of the mast cell and basophil mediators' histamine or total tryptase. Any elevation is consistent with anaphylaxis and indicates that these cells have been activated on a massive scale. These changes may be very transient, and normal levels do not exclude the diagnosis. It is critical to obtain blood samples for measurement of these mediators during specific windows of time after the onset of symptoms. Instructions for proper timing and collection of samples are provided (table 3). The interpretation of elevations in histamine and tryptase are reviewed elsewhere. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)
Acute management — Acute management of venom-induced anaphylaxis is similar to the treatment of anaphylaxis from other causes, with intramuscular injection of epinephrine into the anterolateral thigh being the initial drug of choice.
Rapid overview tables of the initial assessment and treatment of anaphylaxis and dosing of epinephrine in adults (table 4) and children (table 5) are provided. These tables are intended to assist clinicians in emergency department and urgent care settings. Anaphylaxis management is discussed in greater detail separately. (See "Anaphylaxis: Emergency treatment", section on 'Immediate management'.)
The treatment of widespread urticaria, which represents a generalized reaction but does not meet criteria for anaphylaxis, is influenced in part by the patient's age.
●In children under 16 years of age, in whom generalized cutaneous reactions are more common and do not predictably progress to anaphylaxis, treatment with epinephrine need not be given for widespread urticaria. However, epinephrine should be given without delay if the child has symptoms beyond the skin or a history of past sting-induced anaphylaxis. (See 'Natural history of systemic allergic reactions' below.)
●In contrast, epinephrine may be administered to adults with widespread urticaria, as venom reactions can be more severe in this age group. However, use of epinephrine might not be necessary if the patient had a history of other past reactions limited to urticaria.
Discharge care and referral — Prior to discharge from the acute care setting, patients should be informed that venom allergy is a potentially fatal disorder, further evaluation will be needed, and that venom immunotherapy is available to prevent anaphylaxis to future stings.
They should receive:
●An epinephrine autoinjector(s) (supplying at least two doses of epinephrine)
●Instructions on how and when to use epinephrine (see "Patient education: How to use an epinephrine autoinjector (The Basics)" and "Patient education: Using an epinephrine autoinjector (Beyond the Basics)")
●Clear directions to fill the prescription immediately and carry epinephrine at all times
Discharge care for patients with anaphylaxis is reviewed in more detail separately. (See "Anaphylaxis: Emergency treatment", section on 'Discharge care' and "Prescribing epinephrine for anaphylaxis self-treatment".)
Patients suspected of having a systemic allergic reaction following a Hymenoptera sting (of any severity) should be referred to an allergist/immunologist to determine if they are candidates for venom immunotherapy [10]. Providing the patient with a prescription for self-injectable epinephrine is an essential but not sufficient intervention because patients often do not fill the prescription or have the epinephrine on hand when needed and because severe venom anaphylaxis can be refractory even to promptly administered epinephrine [21]. Venom immunotherapy reduces the risk of recurrent life-threatening reactions from 30 to 60 percent to less than 5 percent and is the definitive treatment for venom allergy. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action".)
Natural history of systemic allergic reactions — In patients with confirmed venom allergy who are not treated with venom immunotherapy, the risk of anaphylaxis to a subsequent sting is approximately 30 to 60 percent [41]. Subsequent reactions tend to be of similar or lesser intensity. Less than 10 percent of patients had a more severe reaction on subsequent stings in one series [41]. The impact of venom immunotherapy on the risk of a recurrent systemic reaction is discussed separately. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action".)
Patients with symptoms limited to the skin (eg, urticaria and/or angioedema, even if widespread) are at low risk for future more severe systemic reactions. Children under 16 years of age, specifically, have about a 10 percent chance of future systemic reactions, most of which will also be limited to the skin [14]. The risk in adults is similarly low but not as well-defined [10]. The reasons for this lack of progression over time are not clear.
OTHER UNUSUAL REACTIONS — Rarely, toxic effects are seen with large numbers of simultaneous stings. In addition, Hymenoptera stings occasionally cause delayed-onset, immunologic or idiosyncratic reactions, such as serum sickness or nephritis.
Toxic reactions from numerous stings — The venoms injected by Hymenoptera are toxic and have vasoactive properties that are associated with systemic symptoms. Symptoms include nausea, vomiting, diarrhea, headache, vertigo, syncope, convulsions, and fever. Hemolysis, cardiac complications, renal failure, and rhabdomyolysis have also been described [42,43].
Massive numbers of fire ant stings have been reported in infants and debilitated older adults who could not defend themselves or escape. The evaluation and treatment of such patients is discussed elsewhere. (See "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment", section on 'Massive attacks'.)
Toxic reactions are uncommon, since most stinging events involve one to a few stings, and only a small amount of toxin is injected into the body [42]. However, patients who disrupt a nest or hive can sustain massive envenomation as the insects swarm out in defense. Case reports of toxic reactions mostly involved patients who had sustained hundreds of stings, although renal failure has been described after as few as 20 wasp stings [31,42]. The number of stings associated with a potential 50 percent fatality rate due to direct venom effects (ie, the LD50) has been calculated (based upon animal models) to be 1500 stings for a 75-kg individual [2].
Africanized honey bees, found in South America and the southwestern United States, are no more toxic per sting than other bees [44,45]. However, this species acquired the common name "killer bees" because they can sting in large numbers once provoked [46].
Acute treatment — Acute treatment of a patient with numerous Hymenoptera stings begins with rapid general assessment and prompt removal of any insects entrapped in the patient's clothing, so that additional stings are prevented.
Clinical symptoms dictate pharmacologic management. There are no specific antitoxins available for the treatment of Hymenoptera stings. Some patients have concomitant anaphylaxis and require immediate epinephrine and other appropriate management [43]. Otherwise, care is supportive. The patient should be observed and monitored with serial chemistries, including hemoglobin and myoglobin [42].
Insect venom is highly sensitizing, and individuals who have sustained a toxic reaction after multiple stings may develop positive skin tests to venoms and are at risk for anaphylactic reactions in response to future stings. Referral to an allergy specialist is indicated.
Other uncommon reactions — Occasionally, other types of systemic reactions are reported after insect stings. These include serum sickness, vasculitis, neuritis, myocarditis, and encephalitis [10,47-49]. Onset is typically delayed by days to weeks after the sting, as most of these reactions arise from the tissue deposition of antibody-antigen complexes, which precipitate only after sufficient antibody has been formed.
As an example, serum sickness is usually manifested as urticaria with joint pain, fever, fatigue, and lymphadenopathy 7 to 10 days after the sting [47]. Patients with serum sickness may demonstrate immunoglobulin E (IgE) and immunoglobulin G (IgG) antivenom antibodies [50]. (See "Serum sickness and serum sickness-like reactions".)
The development of cold-induced urticaria has also been noted, beginning days to weeks after Hymenoptera stings [51-53]. Most patients had no adverse reaction to the sting itself.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stinging insect allergy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Anaphylaxis (The Basics)" and "Patient education: How to use an epinephrine autoinjector (The Basics)" and "Patient education: Insect bites and stings (The Basics)" and "Patient education: Insect allergy (The Basics)")
●Beyond the Basics topics (see "Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Anaphylaxis treatment and prevention of recurrences (Beyond the Basics)" and "Patient education: Using an epinephrine autoinjector (Beyond the Basics)" and "Patient education: Bee and insect stings (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Stinging insects – Bees, wasps, yellow jackets, hornets, and imported fire ants are all members of the order Hymenoptera. (See 'Stinging Hymenoptera' above.)
●Uncomplicated local reactions – The most common reaction to Hymenoptera stings is transient pain and redness at the sting site lasting a few hours (local reaction) (picture 5). Local reactions usually do not require treatment. Application of cold compresses can be helpful. (See 'Local reactions' above.)
●Large local reactions – Large local reactions (LLRs) consist of exaggerated swelling lasting a few days (picture 7). LLRs typically require symptomatic treatment to control itching (most prominent with fire ant stings) or minimize swelling. The affected part should be elevated if possible. For severe swelling, we suggest administration of oral prednisone (Grade 2C). A dose of 20 to 60 mg given once or tapered rapidly over two to five days is sufficient. (See 'Treatment' above.)
●Anaphylaxis – Anaphylaxis occurs in up to 3 percent of stings due to allergens in Hymenoptera venoms. Venom-induced anaphylaxis can be particularly severe and is a leading cause of anaphylactic deaths. Anaphylaxis is diagnosed clinically (table 2). Individuals with possible allergy should be questioned carefully about the different symptoms of anaphylaxis, which may be unfamiliar to the patient and not readily reported (table 1). (See 'Systemic allergic reactions/anaphylaxis' above.)
•Treatment of anaphylaxis – The initial treatment of choice for anaphylaxis is epinephrine injected intramuscularly into the anterolateral thigh (table 4 and table 5). (See 'Acute management' above.)
•After care and referral for venom immunotherapy – Upon discharge, any patient with symptoms of a systemic allergic reaction or anaphylaxis should receive both of the following:
-An epinephrine autoinjector and instructions about how and when to use it. (See "Patient education: How to use an epinephrine autoinjector (The Basics)".)
-Referral to an allergy specialist to determine if he/she is a candidate for venom immunotherapy, which is the definitive treatment for venom allergy. Venom immunotherapy reduces the risk of a recurrent life-threatening reaction to a subsequent sting to less than 5 percent. Allergy specialists can also provide patients with detailed advice about strategies for avoidance. (See 'Discharge care and referral' above.)
●Other rare reactions – Occasionally, large numbers of simultaneous stings may result in toxic reactions, which present with different combinations of nausea, vomiting, diarrhea, headache, vertigo, syncope, convulsions, and fever. Hemolysis, cardiac complications, renal failure, and rhabdomyolysis have also been reported. In addition, Hymenoptera stings occasionally cause delayed-onset, immunologic or idiosyncratic reactions, such as serum sickness, nephritis, or cold-induced urticaria. (See 'Other unusual reactions' above.)
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