Hymenoptera Stings

Background

Hymenoptera stings account for more deaths in the United States than any other envenomation. The order Hymenoptera includes Apis species, ie, bees (European, African), vespids (wasps, yellow jackets, hornets), and ants (see the images below). Most deaths result from immediate hypersensitivity reactions and anaphylaxis. Severe anaphylactoid reactions occur occasionally when toxins directly stimulate mast cells. In addition to immunologic mechanisms, some injury occurs from direct toxicity. While the vast majority of stings cause only minor problems, stings cause a significant number of deaths.

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Western paper wasp (Mischocyttarus flavitarsis) building a nest. By Sanjay Acharya (self-made at Sunnyvale, California, USA). Courtesy of Wikimedia Co....

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Yellow jacket. By Richard Bartz, Munich aka Makro Freak (Own work). Courtesy of Wikimedia Commons.

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Fire ants. US Department of Agriculture. Courtesy of Wikimedia Commons.

See Arthropod Envenomation: From Benign Bites to Serious Stings, a Critical Images slideshow, for help identifying and treating various envenomations. See also All About Allergies: Be Ready for Spring, to help identify a variety of allergens and symptoms.

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Pathophysiology

Target organs are the skin, vascular system, and respiratory system. Pathology is similar to other immunoglobulin E (IgE)–mediated allergic reactions. Anaphylaxis is a common and life-threatening consequence of Hymenoptera stings and is typically a result of sudden systemic release of mast cells and basophil mediators.^[1] Urticaria, vasodilation, bronchospasm, laryngospasm, and angioedema are prominent symptoms of the reaction. Respiratory arrest may result in refractory cases.

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Etiology

Hymenoptera are social creatures that typically sting to protect their colony, nest, or hive. Most stings are incited by proximity to the colony. Noisy or vigorous activity (eg, lawn mowers, weed eaters), bright or dark colors, and perfumes also may incite stings. When a colony is disturbed, many Hymenoptera release defense pheromones that attract other members of the colony to sting. These pheromones are released during stinging or when an insect is smashed.

Although bee and wasp venom varies from species to species, all venom is composed primarily of proteins, peptides, and amines. Toxic components include phospholipase, histamine, bradykinin, acetylcholine, dopamine, and serotonin. In addition, mast cell degranulating (MCD) peptide and mastoparan are peptides that can cause degranulation of mast cells and result in an anaphylactoid reaction. Molecule size and the presence of protein enhance the antigen properties of venom, making it a potent activator of the immune system. Most significant reactions are mediated through true IgE allergic mechanisms that activate mast cell degranulation.

Anaphylactoid reactions may occur. However, venom load may be sufficient to cause fatal injury without the added effects of the endogenous system. This may result from as few as 30 vespid stings or 200 honeybee stings. Since the compounds are similar in anaphylactic and toxic reactions, pathology and treatment also are similar.

Bees and wasps sting through a modified ovipositor. They puncture the skin with a hollow stinger and then inject venom. Bees leave their barbed stinger in the skin along with its stinging apparatus, killing the bee. Vespids have smooth or less-barbed stingers and can sting more than once. Vespids are responsible for almost twice as many allergic reactions as honeybees. Retained stingers can cause granuloma formation and subsequent epidermal necrosis.

"Killer" bee is the moniker applied to the Africanized honeybee (Apis mellifera scutellata), which was originally introduced into the New World as a hybrid of European honeybees and a variety of honeybee from Africa. Toxicity from the sting of a single Africanized bee is no worse than the sting of a single European bee. Africanized honeybees show behavioral changes, including increased defensive stinging. One pheromone, isoamylacetate, has been isolated as a mediator of aggressive group-defensive behaviors in Africanized bees. Africanized bees defend their hive up to a 150-yard radius, three times the distance of European bees. As of May 2000, Africanized bees have migrated from their western-hemisphere origin in Brazil to Texas, Arizona, California, New Mexico, Nevada, Utah, Alabama, Louisiana, Arkansas, Oklahoma, and Florida, according to the US Department of Agriculture.^[2] Multiple stings from these species are more common. Honeybees fly at only 4 mph, allowing most victims to flee after only a few stings. Overwhelming numbers of stings usually occur in young patients or in those slowed by physical limitations or intoxication.

In addition to reaction to stings, bee venom may be encountered as a result of apiotherapy, a modality used in traditional Chinese medicine. In this treatment, ointment containing bee venom is applied to skin or eye and may result in an immunologic reaction.

Ant stings

Ants account for one half of all insects. While many ant species sting, the most aggressive in the United States are imported fire ants, Solenopsis invicta. These ants fiercely guard their territory and attack intruders in large numbers, inflicting thousands of stings and bites to victims unable to escape. Fire ant venom is 95% alkaloid, which is unique among ants. A fire ant typically bites with its mandibles, then swivels its abdomen and stings repeatedly in an arc about the bite site. Their stings develop into sterile pustules and then rupture, leaving crusted wounds that may become infected secondarily. Patients have survived as many as 5000 fire ant stings. Brazilian fire ants, S invicta, have nearly eradicated native ant species in their range from Florida to Texas and north to Arkansas and South Carolina. S invicta is found in South and North America in areas where mean high temperatures are 15°C or higher.

Stings from other ants often closely resemble those of wasps and bees, although with less tissue destruction and less severity. Harvester ants, Pogonomyrmex species, inject venom containing a hemolysin. This sting frequently creates an ecchymotic area surrounding the sting site. Some species of field ants truly bite with the mandible and spray the acidic toxin into the wound without injecting venom. Formic acid, a component of ant venom uncommon in bee or wasp stings, is derived from the superfamily name Formicidae. Ant stings cause generalized reactions less often than stings from flying Hymenoptera.

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Epidemiology

Frequency

United States

Ants sting 9.3 million people each year. Other Hymenoptera species account for more than 1 million stings annually. Anaphylaxis secondary to Hymenoptera envenomation affects roughly 3% of the general population.^[3] Systemic reactions leading to life-threatening manifestations occurs in approximately 0.4-0.8% of children and 3% of adult patients.^[4]

According the US Bureau of Labor Statistics, from 2003 to 2010, bees accounted for 52 fatal occupational injuries, wasps/yellow jackets 14, and ants 4^[5] . Additionally, fatal occupational injuries involving insects, by year, are as follows^[5] :

• 2003: 6 deaths
• 2004: 10 deaths
• 2005: 15 deaths
• 2006: 10 deaths
• 2007: 11 deaths
• 2008: 10 deaths
• 2009: 9 deaths
• 2010: 12 deaths

International

A 2009 study from Costa Rica reported on Hymenoptera sting fatalities over a 22-year period (1985-2006). The annual number of deaths varied from 0-6 (2.4 deaths/year average), with a total of 52 deaths over the study period. Most deaths were in older (>50 years) and younger (< 10 years) males.^[6]

From 1979 through 1998, 7 fatalities from wasp stings were reported in Australia, all from rural areas; 5 of the 7 had a history of wasp or bee venom allergy.^[7]

Race

No race predilection exists.

Sex

Hymenoptera stings of all types are more common in males than in females, probably because of more frequent exposure.

Age

Although most deaths from toxic reactions occur at extremes of age, frequency of bites is not age dependent. Peak incidence of death from anaphylaxis is in people aged 35-45 years.

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Prognosis

Most stings resolve with no residual complaints. Large local reactions do not predispose patients to generalized reactions in the future. Less severe generalized reactions precede most fatal reactions.

Large local reactions occur in 17-56% of those stung. In one study, 1-2% experienced a generalized reaction, and 5% sought medical care. Individuals with large local reactions have a 5-10% risk of subsequent development of a severe systemic reaction if re-stung.^[4]

An updated review of animal-related deaths in 2005 determined that Hymenoptera stings accounted for 533 deaths in the United States from 1991-2001. This number represented 70.2% of all venomous animal-related fatalities in the United States during this period.^[8]

In 1989, 32 deaths were reported from fire ant stings in Texas, Florida, Louisiana, and Georgia.^[9]  

Wasps and bees cause 30-120 deaths yearly in the United States.

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Patient Education

Educate all patients on how to avoid stings.

For patient education resources, see the Bee and Wasp Stings Center, Environmental Exposures and Injuries Center, Allergy Center, and Allergic Reaction and Anaphylactic Shock Center, as well as Bee and Wasp Stings and Severe Allergic Reaction (Anaphylactic Shock).

For related information, see Medscape's Allergy Resource Center.

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History

A patient's reaction to a Hymenoptera sting determines the treatment required. Reactions may be graded as local, urticaria without systemic symptoms, and generalized. Emergency physicians should attempt to determine degree of reaction based on both patient history and a physical examination.

Rapid onset of symptoms is the rule; 50% of deaths occur within 30 minutes of the sting, and 75% occur within 4 hours.

Fatal allergic reactions can occur as the first generalized reaction. Far more common, however, is a fatal reaction following a previous, milder generalized reaction. The shorter the interval since the last sting, the more likely it is that a severe reaction will take place.

Large local reactions do not predispose patients to generalized reactions. Local reactions may be life threatening if local swelling at the sting site compromises the airway. Local reactions to stings can cause peripheral nerve block.

Local reactions may produce the following:

• Pain occurs immediately after sting.
• Edema is marked and may extend to 10 cm from site of envenomation.
• The insect frequently is seen by patient and may be identified from the description.
• Bleeding may occur at site of sting.
• Pruritus is common.
• Vasodilation may produce a sensation of warmth.
• The stinging apparatus may have been seen in the wound and removed prior to presentation.
• Nausea or vomiting may occur without generalization.
• If Hymenoptera are swallowed, stings can cause painful swelling in the mouth or esophagus.
• Visceral pain may occur with stings in the gastrointestinal (GI) tract after ingestion of the insect.

Urticaria may occur with or without the symptoms noted in local reaction.

Generalized reactions may produce the following symptoms:

• Urticaria
• Confluent red rash
• Shortness of breath, wheezing
• Edema in airway, tongue, or uvula
• Weakness, syncope
• Anxiety, confusion
• Chest pain

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Physical Examination

Local reactions may include the following:

• Erythema, edema, warmth, tenderness
• Drainage from site of sting
• Compromised distal circulation as result of edema
• Distal sensation loss from stings over peripheral nerve
• Corneal ulceration from corneal stings
• With bee stings, stinging apparatus visible at sting site
• If Hymenoptera are swallowed, painful swelling in the mouth or esophagus
• Ant stings: Vesicles from fire ants, classic arc of fire ant stings, and ant stings on mucous membranes or conjunctival surfaces cause dramatic swelling in patients who are sensitive. See the image below.
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Urticaria or generalized redness may develop without systemic symptoms.

Generalized reactions may include the following symptoms:

• Urticaria
• Vomiting
• Wheezing
• Tachypnea
• Hypotension
• Laryngoedema, lingular edema, uvular edema
• Delirium, shock
• Respiratory arrest

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Complications

Sting sites may become infected. Infection is more common in fire ant stings because they frequently are multiple; stings vesiculate and then ulcerate, leaving pruritic open wounds.

Rebound anaphylaxis may occur in patients with generalized reactions as antihistamine and alpha-agonist levels subside after treatment.

Anaphylaxis may occur in susceptible patients from exposure to other insect-related material, including honey and apiotherapy.

Serum-sickness-type reactions may occur up to 14 days after a sting.

Myocardial infarction,^[10] renal failure, DIC, rhabdomyolysis,^[11] and cerebral edema may occur after a bee sting.^[12] One case report documents transient inferior ST-segment elevation consistent with myocardial ischemia after a single wasp sting in a 58-year-old man.^[13]  In a retrospective analysis of medical records from 1985-2007, 7 of 45 pediatric patients were noted to have developed acute renal failure after a wasp sting.^[14]

Peripheral nerve block may occur if sting is near the path of a nerve.

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Laboratory Studies

Diagnosis usually is confirmed by patient's history. In systemic reactions, laboratory studies may help evaluate organ damage caused by the reaction. Complete blood cell (CBC) count and blood chemistry may be needed.

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Procedures

Stinger removal

The stinger most commonly appears as a dark barb in the skin with attached stinging apparatus of honeybees.

People who have been stung should remove the bee stinger as quickly as possible. Removal method is not as important as rapidity because the stinging apparatus actively injects venom into the wound for 1 minute after the sting, even if the bee has been killed or knocked away from the site. Visscher and colleagues demonstrated no advantage to scraping away the stinger compared with pinching.^[15]

Forceps may be needed to remove the stinger after the venom sac has been torn away.

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Prehospital Care

Prehospital care must assess severity immediately and provide immediate appropriate treatment, because the most endangered patients die within 30 minutes of a sting.

Local reactions can be life threatening if swelling occludes the airway. Initiate invasive measures to secure the airway if this occurs. Otherwise, the following local care measures suffice:

• Provide supplemental oxygen
• Diphenhydramine limits the size of the local reaction.
• Clean the wound and remove the stinger if present.
• Apply ice or cool packs.
• Elevate the extremity to limit edema.

Manage generalized reactions similarly to anaphylaxis, even in the absence of shock. Increased vascular permeability in anaphylaxis may result in transfer of 50% of the intravascular fluid into the extravascular space within 10 minutes.^[1] Check airway and ventilatory status. Treatment should include an initial intravenous (IV) bolus of 10-20 mL/kg isotonic crystalloids in addition to diphenhydramine and epinephrine.

If the patient has not removed the stinger, it should be removed as soon as possible by the first caregiver on the scene. Delay increases venom load, so the fastest removal technique is the best. Pinching and traction is an acceptable technique.

EMT or self-administration of intramuscular or subcutaneous epinephrine should be initiated immediately in the event of severe reaction. Intramuscular epinephrine injections into the lateral thigh provide more rapid absorption and higher plasma epinephrine levels than intramuscular or subcutaneous injections administered in the arm.^[1]

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Emergency Department Care

Epinephrine is the mainstay of treatment for anaphylaxis. Corticosteroids should be administered in severe cases of envenomation, with the caution that steroids do little to improve symptoms acutely and no definitive evidence exists that corticosteroids reduce recurrent or prolonged anaphylaxis.^[16]

H2 blockers such as ranitidine and cimetidine may be given intravenously.^[17] Administration of one of these medications combined with diphenhydramine is superior to diphenhydramine alone.^[1]

In cases of refractory anaphylaxis, glucagon may be helpful if concomitant beta-blockers are preventing adequate response to epinephrine treatment.^[1]

Vasopressors such as epinephrine or dopamine can be used to provide vascular support.

Patients developing respiratory arrest require ventilatory support.

Blood products may be required in the event of disseminated intravascular coagulation (DIC).

Repeated doses of epinephrine may be indicated for severe cases.

In the event of cardiopulmonary arrest due to anaphylaxis, intravenous epinephrine should be administered as a first-line agent.^[1]

Consider further inpatient care for all patients with life-threatening reactions. Observe for sufficient duration to ensure symptoms do not rebound after initial treatment. Rebound phenomena may occur up to 12 hours after sting. Respiratory and circulatory support may be needed if secondary organ damage has occurred.

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Consultations

Refer all patients with generalized reactions to an allergist as soon as possible, because risk of fatal reaction is inversely related to length of time since the last sting.

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Prevention

Avoiding stings is vitally important for persons who are hypersensitive. Whenever these patients are outdoors, they should adhere to the following suggestions:

• Avoid using perfumes or hygiene products that include perfumes, as these may attract flying Hymenoptera.
• Avoid wearing bright colors.
• Avoid known hive or nest locations.
• Do not use noisy equipment such as lawn mowers, edgers, or blowers within 50 yards of beehives or 150 yards of Africanized bee colonies.
• Do not flail arms when confronted by bees or wasps because smashing one often incites others to sting.

Following severe reactions, individuals should be referred to an allergist/immunologist for potential immunotherapy and desensitization. Administration of venom-specific immunotherapy (VIT) is an established mode of treatment and offers long-term protection in 85-95% of cases.^[3] New research on anti-immunoglobin (Ig) E antibody has shown promising results as a combination therapy for those unable to tolerate standard VIT.^[3] A literature review and case report from 2014 suggest that adjunctive treatment with omalizumab can improve symptoms in patients with mastocytosis on VIT therapy.^[18]

Guidelines on hymenoptera venom allergy immunotherapy have been issued by the European Academy of Allergy and Clinical Immunology.^[19] They are summarized as follows:

• VIT recommended in adults with systemic sting reactions confined to generalized skin symptoms if quality of life is impaired
• VIT recommended in children and adults with detectable sensitization and systemic sting reactions exceeding generalized skin symptoms
• VIT not recommended in individuals with incidentally detected sensitization and no systemic symptoms
• Factors not considered a higher risk of adverse events are severe initial sting reaction, high skin-test reactivity, and high venom-specific IgE levels
• Pretreatment with H1 antihistamines recommended; reduces large local reactions and, to some extent, systemic adverse events
• Recommended VIT duration is at least 3 years; 5 years recommended in patients with severe initial sting reactions
• Lifelong VIT may be recommended in the following: (1) highly exposed patients with honeybee venom allergy, (2) patients with very severe initial sting reactions (Muller grade IV or grades III-IV, according to Ring and Messmer), and (3) patients with systemic adverse effects during VIT, as they are major risk factors for relapse
• All available diagnostic tests, including determination of venom-specific IgE, IgG, basophil activation testing response, and allergen-blocking capacity, are not capable of estimating the individual risk for relapse
• Most reliable method to evaluate effectiveness of VIT is sting challenges

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Long-Term Monitoring

Refer all patients with generalized reactions for allergy testing and desensitization, if indicated. Provide means to self-administer epinephrine and diphenhydramine to all patients with generalized reactions, and advise them to wear medic alert bracelets.

Continue treatment with steroids in the ED for 3-5 days. Continue administering antihistamines for at least 24 hours continuous dosing.

Cool sting sites for 12 hours. Keep extremities with stings elevated for 12 hours when development of edema may present difficulties.

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Medication Summary

Medications used to treat Hymenoptera stings include antihistamines (H1, H2), steroids, alpha- and beta-receptor agonists, and bronchodilators.

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Diphenhydramine (Benadryl, Aler-Dryl, Diphen, Genahist, Altaryl)

• Dosing, Interactions, etc.

Clinical Context:  Diphenhydramine is the drug of choice for all stings. It is an H1 and partial H2 receptor blocker used for symptomatic relief of allergic symptoms caused by histamine released in response to allergens.

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Hydroxyzine (Vistaril)

• Dosing, Interactions, etc.

Clinical Context:  Hydroxyzine antagonizes H1 receptors in the periphery and may suppress histamine activity in the subcortical region of the central nervous system (CNS). This agent is used to manage histamine-mediated pruritus; it is an alternative to diphenhydramine.

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Class Summary

These drugs directly block effects of some venom and effects of endogenously released histamine.

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Albuterol (Proventil HFA, Ventolin HFA, ProAir HFA, VoSpire ER)

• Dosing, Interactions, etc.

Clinical Context:  Albuterol is an adjunctive treatment for bronchospasm given by nebulization, and it is a beta-agonist useful to treat bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by action on beta2-receptors and has little effect on cardiac muscle contractility.

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Class Summary

Epinephrine causes vasoconstriction, bronchodilation, and increased cardiac output. The effects of albuterol and theophylline are more focused on bronchodilation.

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Methylprednisolone (Solu-Medrol, Depo-Medrol)

• Dosing, Interactions, etc.

Clinical Context:  Methylprednisolone may be useful in cases of generalized reaction unless contraindications exist. It may decrease inflammation in inflammatory and allergic reactions by reversing increased capillary permeability and suppressing PMN activity.

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Prednisone (Deltasone, Prednisone Intensol, Rayos)

• Dosing, Interactions, etc.

Clinical Context:  Prednisone, a commonly used oral agent, may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It must be metabolized to the active metabolite prednisolone for it to have an effect. Conversion may be impaired in liver disease.

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Prednisolone (Orapred, Millipred, Millipred DP, Veripred 20)

• Dosing, Interactions, etc.

Clinical Context:  Prednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity.

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Class Summary

These drugs act to stabilize lymphocytes and to reduce release of endogenous vasoactive compounds.

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Glucagon (Glucagen HypoKit, Glucagon Emergency)

• Dosing, Interactions, etc.

Clinical Context:  Glucagon is the drug of choice for severe anaphylaxis in patients taking beta-blockers (should be used in addition to epinephrine, not as a substitute).

Pancreatic alpha cells of the islets of Langerhans produce glucagon, a polypeptide hormone. It exerts the opposite effects of insulin on blood glucose. Glucagon elevates blood glucose levels by inhibiting glycogen synthesis and enhancing the formation of glucose from noncarbohydrate sources, such as proteins and fats (gluconeogenesis). It increases hydrolysis of glycogen to glucose (glycogenolysis) in the liver in addition to accelerating hepatic glycogenolysis and lipolysis in adipose tissue. Glucagon also increases the force of contractions in the heart and has a relaxant effect on the GI tract.

The dose used for anaphylaxis is higher than the usual dose of 1 mg (1 U) IV/IM/SC used to treat hypoglycemia.

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Class Summary

Glucagon acts in the adipose tissue and liver to quickly stimulate gluconeogenesis, and thereby elevate blood glucose levels.

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Epinephrine (Epi-Pen, Adrenaclick, Adrenalin, Adyphren)

• Dosing, Interactions, etc.

Clinical Context:  Epinephrine is the drug of choice for systemic reactions. It has alpha-agonist effects that increase peripheral vascular resistance and reverse peripheral vasodilation, systemic hypotension, and vascular permeability. Conversely, the beta-agonist activity of epinephrine produces bronchodilation, chronotropic cardiac activity, and positive inotropic effects. Epinephrine may be self-administered through auto-injectors.

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Class Summary

Sympathomimetic agents produce direct or indirect stimulation of adrenergic receptors and have various actions, depending on the specific receptors involved.

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Cimetidine (Tagamet HB)

• Dosing, Interactions, etc.

Clinical Context:  Cimetidine is indicated for systemic reactions that do not respond completely to diphenhydramine, or when severity indicates a need for maximal treatment.

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Famotidine (Pepcid, Heartburn Relief, Acid Reducer)

• Dosing, Interactions, etc.

Clinical Context:  Famotidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.

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Ranitidine (Zantac, Deprizine FusePaq, Deprizine RapidPaq, Zantac 75)

• Dosing, Interactions, etc.

Clinical Context:  Ranitidine is a competitive, reversible inhibitor of histamine at the H2 receptor that may be used in conjunction with H1-blockers for severely symptomatic cases. It has fewer drug interactions than cimetidine and may be better for patients who take other medications metabolized by the cytochrome p450 system.

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Class Summary

These agents block H2 receptors of gastric parietal cells, leading to inhibition of gastric secretions. They can also be used in combination with H1 blockers for patients with severe histamine reactions that do not respond to H1 blockers alone.

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Theophylline (Theo-24, Elixophyllin, Theocron)

• Dosing, Interactions, etc.

Clinical Context:  Theophylline is used to relieve bronchospasm in resistant cases. It acts to decrease muscle tone in both small and large airways in the lungs, thus increasing ventilation. Efficacy in managing bronchodilation may be due to its potentiation of exogenous catecholamines, stimulation of endogenous catecholamine release, and diaphragmatic muscular relaxation. Its effects as a bronchodilator usually are seen at levels considered to be toxic (>20 mg/dL).

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Class Summary

These agents are used as additional therapy for patients who remain in refractory status of bronchospasm despite maximal inhalational therapy and the use of corticosteroids. These medications may be administered intravenously.

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