AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

In the United States alone, anaphylaxis accounts for approximately 500 deaths each year and significant morbidity. Hymenoptera envenomation is a major contributor to these statistics.

The order Hymenoptera includes bees, hornets, wasps, yellow jackets, and ants. More than 14,000 species are represented. Honeybees and bumblebees belong to the Apidae family, while hornets, wasps, and yellow jackets belong to the Vespidae family. Ants belong to the family Formicidae.

Among winged Hymenoptera, envenomation is used for killing or paralyzing prey and for defense. The stinger, therefore, is used repeatedly. Only the honeybee leaves the stinger, venom gland, and other internal organs attached at the site of the sting.

Hymenoptera are present on all land areas of the world, except the polar regions, during some or all seasons. In Africa, domesticated honeybees have been crossed with more aggressive wild honeybees. These Africanized bees (Apis mellifera scutellata) have been introduced into South America and, from there, have migrated to North America, including the southern United States. Their venom is no more potent than that of other honeybees, but they are more aggressive and tend to swarm, causing multiple stings.

Fire ants (Solenopsis invicta) also are present in the southern United States, having migrated from South America. In Florida and Louisiana, they have replaced many of the indigenous species.

Pathophysiology

The venom of winged Hymenoptera contains over 30 individual compounds. These include biogenic amines (eg, acetylcholine, dopamine, histamine, norepinephrine, serotonin), polypeptides or protein toxins (eg, apamin, melittin, kinins), and enzymes (eg, hyaluronidase, phospholipases). The venom of fire, or stinging, ants consists of small amounts of low molecular weight protein and is as much as 95% alkaloid, which is uncommon in ant species.

Reactions to envenomation may be directly toxic, either local or systemic, or allergic, either localized or anaphylactic. Allergic reaction to fire ant venom is unusual. Strong cross-reactivity to the allergic reactions occurs within a family, but less so between families. The venom of bees and wasps has been reported to be more potent during the autumn months.

Frequency

United States

Hymenoptera envenomation affects nearly every person during his or her lifetime and 10-20% of the population annually. From 300-500 deaths occur annually, almost all are secondary to anaphylaxis.

International

The international incidence of Hymenoptera envenomation is related to region and local custom. In Africa, the harvesting of honey involves collecting honey from wild bees, which usually involves destroying the hive and results in subsequent exposure to hundreds of bees. In traditional Chinese herbal medicine, apiotherapy involves mixing bee venom with ointment and applying it to the skin or eyes, which may result in allergic reactions.

Age

Children with a history of severe reaction may have only slightly higher risk of anaphylaxis when they reach adulthood compared to the general population, while history of severe reaction as an adult is associated with a rate of anaphylaxis of approximately 60%.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Clinical presentation following envenomation by Hymenoptera species follows 3 basic patterns.

• First and most common is the simple sting or local reaction, which initially results in localized swelling and pain, with pruritus following a few hours later. The swelling may increase over several days and may take as long as a week to resolve completely.
• • If the envenomation is on the hands (or in some cases on the feet if toe rings are worn), rings should be removed promptly before the swelling extends to the digits. Swelling may involve an entire extremity.
  • Large envenomations (>30-40 stings) may result in a systemic, or anaphylactoid, reaction with shock secondary to myocardial depression and vasodilation. This is the direct result of systemic absorption of venom and should be distinguished from the allergic reactions discussed below. These patients present with stupor or coma and seizures. They may develop other complications of shock, including metabolic acidosis and organ failure, particularly acute renal failure.
• The second type of presentation is the immediate hypersensitivity reaction, or generalized reaction/anaphylaxis. It may manifest as local swelling or urticaria with pain and itching. It also may spread to become more generalized, with urticaria and itching.
• • The reaction may progress to involve the upper or lower airway in an anaphylactic reaction. If anaphylaxis develops, it usually presents within 1-2 hours but may be delayed for as long as 4-6 hours. Patients treated for anaphylaxis may have recurrent symptoms as long as 48 hours after successful initial treatment.
  • These patients may present with acute airway obstruction due to laryngeal edema or bronchoconstriction with respiratory failure, and early endotracheal intubation or cricothyroidotomy may be necessary. Such patients may not be able to give a history at the time of presentation. If patients present awake and alert, more conservative treatment may be successful, but the clinician is advised to take symptoms such as hoarseness or shortness of breath seriously even in the absence of clinical signs.
  • Early in the treatment of patients presenting with severe local or systemic reaction, while they still are able to provide information, questioning them about their medical history, including medication and allergies, is a wise practice.
  • Patients with a previous history of severe local reactions have a 5% chance of anaphylaxis in the future, while those with generalized systemic reactions have 60% chance of anaphylaxis upon future exposure. More recent and more severe previous reactions are associated with increased risk; however, most patients who die of anaphylaxis give no history of prior severe local or generalized reaction.
• Finally, patients may present with delayed hypersensitivity reactions. These may be immune-complex mediated (either immunoglobulin M or immunoglobulin G) and may be systemic (serum sickness type) or local (Arthus type).
• • Presentation usually is within 1 week of envenomation, but often the history of an insect bite or sting is not volunteered by the patient unless the clinician specifically asks.
  • The symptoms may include fever, arthralgias and myalgias, headache, and general malaise. Signs include rash (either maculopapular or palpable purpura of vasculitis), joint swelling and tenderness with or without effusions, adenopathy, and evidence of glomerulitis or nephrotic syndrome. Necrotizing vasculitis also may be evident.
• Several syndromes, presumed to be immune-mediated, are associated with late complications of Hymenoptera envenomation, including hemolytic anemia, thrombocytopenic purpura, Guillain-Barré syndrome, multiple sclerosis, optic neuritis, Parkinsonism, and transverse myelitis.
• At least 1 case of Münchausen syndrome has been reported, in which a patient with known allergy to aspirin took this drug in order to mimic anaphylaxis from Hymenoptera envenomation.¹
• The stings of fire ants usually are multiple.
• • The presentation usually is that of swelling and pain with early vesicle formation, followed by ulceration and possible secondary infection.
  • Local reactions are the rule, and allergic manifestations, either immediate or delayed, are uncommon.

Physical

• In the presence of a local reaction, one should expect to find local swelling and tenderness at the site(s) of envenomation, but the presence of urticaria may suggest a more generalized reaction.
• • The airway should be accessed in all patients, particularly those with stings to the face or generalized urticaria.
  • Frequently, auscultation of the lungs for the presence of wheezing is advisable, with prompt therapy initiated and reassessed until improvement is noted. If airway involvement is present, an anaphylactic reaction should be considered.
• The physical findings in cases of anaphylactoid reactions resulting from large venom loads are shock with hypotension secondary to vasodilation and myocardial depression. A bradycardia may be present. Stupor or coma is common.
• The physical examination findings in cases of immediate hypersensitivity usually include urticaria and swelling at the site of the sting, which frequently is generalized.
• • Patients often are anxious, but true confusion or stupor should suggest impending respiratory arrest or vascular collapse.
  • Vital signs often show tachycardia and hypertension in addition to an increase in the respiratory rate. The absence of such findings in a patient in obvious distress should suggest impending collapse that requires aggressive intervention.
  • Signs of upper airway obstruction with stridor or lower tract involvement with wheezing may be present.
  • Intercurrent medications, particularly beta-blockers, may mask the signs of anaphylaxis and may complicate its treatment.
  • Both severe systemic reactions and anaphylactic reactions may be complicated acutely by myocardial infarction or stroke and should be investigated further if symptoms suggest these possibilities.
• The physical findings in patients with delayed hypersensitivity are those of the particular syndrome at presentation.
• • Joint effusions and inflammation (serum sickness), palpable purpura (vasculitis), edema or congestive heart failure (renal failure or nephrotic syndrome), and jaundice or bruising (hemolytic anemia or thrombocytopenia) are examples.
  • Neurologic syndromes vary greatly in their specific findings.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Hypersensitivity nephropathy

Any patient presenting with anaphylaxis, particularly after outdoor activities and during the appropriate season, should be questioned (if possible) about an insect sting. If the patient is unconscious, close inspection for a sting and stinger should be performed, and the stinger should be removed.

Patients presenting with a syndrome consistent with a delayed hypersensitivity type reaction should have Hymenoptera envenomation considered in the differential diagnosis, although this seldom alters further workup and management.

Other etiologies of anaphylaxis (eg, drugs, food) should be considered, particularly if the presence of a sting cannot be verified.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Laboratory evaluation usually is not helpful in routine cases of Hymenoptera envenomation.
• In more severe acute reactions, the white blood cell count may be elevated.
• In the presence of shock, coagulopathy or renal failure may be evident and screening for disseminated intravascular coagulation should be performed. Also, an electrolyte battery, BUN determination, creatinine determination, and urinalysis should be performed. An electrocardiogram and cardiac enzymes should be considered in shock that is unresponsive to usual measures in order to help rule out myocardial infarction.
• Delayed hypersensitivity reactions require a workup specific to the presenting syndrome.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• The treatment of simple envenomations seldom requires more than local care.
• • Ice usually is helpful, and pain control can be achieved with ibuprofen or acetaminophen.
  • Narcotics occasionally may be necessary.
  • Itching can be controlled with topical or oral antihistamines.
  • If the stinger is present, it should be removed promptly to avoid continued envenomation. This is best accomplished by scraping with a scalpel or flat card. Using tweezers may squeeze the attached venom sack, injecting more venom.
• Acute Hymenoptera envenomations with generalized reactions, urticaria, or other systemic signs usually require parenteral therapy with antihistamines (diphenhydramine) and/or epinephrine.
• • Prompt and repeated use of epinephrine may be lifesaving and should be administered as often as every 20-30 minutes, if needed, or even by continuous intervenous infusion.
  • Inhaled bronchodilators may be useful in cases where bronchospasm is resistant to epinephrine or where preexisting asthma is exacerbated by the envenomation.
  • The use of corticosteroids parenterally or orally may be useful in long-term management.
  • Addition of an H2 histamine receptor-blocking drug to the H1 antihistamine regimen may assist in controlling urticaria and itching.
  • Liberal use of crystalloid intravenously, and even pressors in cases of shock (anaphylactoid or anaphylaxis), may be necessary.
  • Increased doses of epinephrine or other pressor agents may be necessary if patients are taking beta-blockers or calcium channel blockers.
  • If narcotics are necessary for control of pain in cases of anaphylaxis, fentanyl is the preferred agent because it is not associated with the release of endogenous histamine as are other narcotics, particularly meperidine.
  • Respiratory distress may develop very rapidly, and airway management is critical and should not be delayed if obvious clinical deterioration occurs.
  • If laryngeal edema is present, endotracheal intubation may be difficult or impossible and cricothyroidotomy or tracheotomy may be necessary emergently.
  • If a generalized reaction or anaphylaxis does not resolve with treatment, consideration should be given to in-hospital observation in a monitored unit.
• The management of delayed hypersensitivity reactions is dictated largely by the presentation.
• • In these cases, considering the possibility of Hymenoptera envenomation as an etiology is necessary because envenomations are seldom obvious.
  • The prognosis may be improved if envenomation is the cause, but therapy is unchanged.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Adrenergic agonist agents

These agents relieve reversible bronchospasm by relaxing smooth muscles of the bronchi.

Drug Category: Antihistamines

Act by competitive inhibition of histamine at H1 receptor. This mediates the wheal and flare reactions, bronchial constriction, mucous secretion, smooth-muscle contraction, edema, hypotension, CNS depression, and cardiac arrhythmias.

Drug Category: Corticosteroids

Decrease late immune-mediated complications.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• If patients with anaphylaxis require admission for treatment or observation, it should be to a monitored unit.
• Anaphylaxis may recur as long as 48 hours after presentation and initial treatment.
• Antihistamines and steroids (either parenteral or oral) should be continued.
• Additional doses of epinephrine may be required, or in rare cases, a continuous infusion may be necessary.
• Attention to airway management is critical.
• Discharge is possible after the patient is stable for 24 hours.

Further Outpatient Care

• Following successful treatment of Hymenoptera envenomation, the patient should be referred to his or her primary care physician for follow-up evaluation.
• Continued H1 antihistamines with the addition of an H2 blocker usually controls symptoms. The use of a short (3-5 d) course of corticosteroids (40-60 mg/d prednisone) may be helpful in preventing recurrent anaphylaxis.
• If the reaction was severe or anaphylaxis was present, a self-injecting epinephrine device (eg, EpiPen) and instructions on its use should be given to the patient. Any patient who uses this device should be instructed to go immediately to the nearest emergency department following injection.
• Referral to an allergist for desensitization therapy also is advisable in these cases. Successful desensitization therapy to prevent future anaphylaxis following Hymenoptera envenomation has been well documented.

In/Out Patient Meds

• A self-injecting epinephrine kit may be lifesaving and should be given to all patients who have anaphylactic or severe local or systemic reactions.
• Antihistamines (diphenhydramine) are useful for symptomatic control of itching and swelling. They may be combined with H2 blockers (cimetidine) to increase effectiveness.
• Corticosteroids (prednisone) may decrease the duration and severity of local reaction or prevent the recurrence of anaphylaxis.
• Antibiotics generally are not necessary unless infection is apparent. They have no prophylactic role.

Complications

• Infection rarely complicates a local sting, but, in such cases, antibiotics or local incision and drainage may be necessary.
• Recurrent anaphylaxis after initial successful treatment is fairly common.
• • Admission to a monitored unit should be strongly advised in these situations.
  • Treatment is the same as that of the initial episode.
  • Reexamine the site of the sting to be sure the stinger was not inadvertently left after the first evaluation and treatment.
• Prolonged shock after anaphylactoid or anaphylactic reactions may result in myocardial infarction, stroke, acute renal failure, or other ischemic injuries.
• • The clinician should be aware of this possibility and take appropriate steps to investigate and treat these conditions should they develop.
  • This is particularly true in the patient who is comatose or intubated and unable to report symptoms.

Patient Education

• In patients with severe or anaphylactic reactions, eduction directed toward prevention of future anaphylaxis is a very important part of the discharge plan.
• • The patient should be provided with a self-injecting epinephrine device and instructions on its use. The patient should be advised to proceed directly to an emergency department if this device is used.
  • Patients also should be advised on techniques useful for avoiding future stings, including avoiding Hymenoptera, if possible, and avoiding perfumes and brightly colored clothes when outside.
• For excellent patient education resources, visit eMedicine's Bee and Wasp Stings Center and Environmental Exposures and Injuries Center. Also, see eMedicine's patient education article Bee and Wasp Stings.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose anaphylaxis and to initiate appropriate therapy may be a potential legal issue. The clinician should consider anaphylaxis in any envenomation.
• Failure to remove the insect's stinger is also a potential problem. Examine all patients for the presence of a venom sac, and remove it if present.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Hendrix S, Sale S, Zeiss CR, Utley J, Patterson R. Factitious Hymenoptera allergic emergency: a report of a new variant of Munchausen's syndrome. J Allergy Clin Immunol. Jan 1981;67(1):8-13. [Medline].
2. Ginsburg CM. Fire ant envenomation in children. Pediatrics. May 1984;73(5):689-92. [Medline].
3. Golden DB, Valentine MD, Kagey-Sobotka A. Regimens of Hymenoptera venom immunotherapy. Ann Intern Med. May 1980;92(5):620-4. [Medline].
4. Gruchalla RS. Immunotherapy in allergy to insect stings in children. N Engl J Med. Aug 12 2004;351(7):707-9. [Medline].
5. Ingall M, Goldman G, Page LB. Beta-blockade in stinging insect anaphylaxis. JAMA. Mar 16 1984;251(11):1432. [Medline].
6. Lazoglu AH, Boglioli LR, Taff ML. Serum sickness reaction following multiple insect stings. Ann Allergy Asthma Immunol. Dec 1995;75(6 Pt 1):522-4. [Medline].
7. Li JT, Yunginger JW. Management of insect sting hypersensitivity. Mayo Clin Proc. Feb 1992;67(2):188-94. [Medline].
8. Mauriello PM, Barde SH, Georgitis JW. Natural history of large local reactions from stinging insects. J Allergy Clin Immunol. Oct 1984;74(4 Pt 1):494-8. [Medline].
9. Reisman RE. Insect stings. N Engl J Med. Aug 25 1994;331(8):523-7. [Medline].
10. Reisman RE. Natural history of insect sting allergy: relationship of severity of symptoms of initial sting anaphylaxis to re-sting reactions. J Allergy Clin Immunol. Sep 1992;90(3 Pt 1):335-9. [Medline].
11. Reisman RE. Unusual reactions to insect venoms. Allergy Proc. Nov-Dec 1991;12(6):395-9. [Medline].
12. Wagdi P, Mehan VK, Burgi H. Acute myocardial infarction after wasp stings in a patient with normal coronary arteries. Am Heart J. Oct 1994;128(4):820-3. [Medline].

Article Last Updated: Nov 8, 2007