sign in sign up
<<
Home , Bee sting, Latrodectus bishopi

Emergency Department Evaluation and Treatment for Children With Envenomations: Immunologic and Toxicologic Considerations Cyrus Rangan, MD, FAAP, ACMT

Arthropod envenomations are a significant cause of environmental injury in children. , , and inflict injury via specialized with a broad range of components, mechanisms, and potential treatments. Immunologic and toxicologic considerations in the evaluation and management of arthropod envenomations are important for the under- standing of the progression of envenomations, prompt diagnosis of severe conditions including , and the use of antivenom in selected cases. Clin Ped Emerg Med 8:104-109 ª 2007 Published by Elsevier Inc.

KEYWORDS envenomation, arthropod, arachnida,

rthropod bites and stings accounted for more than ever, clinical symptoms of envenomation and treatment A75000 reports to control centers in the are similar. Bees are attracted to carbon dioxide (hence, United States in 2005 [1]. The phylum Arthropoda the predilection for bees to fly around the facial area), includes 2 clinically important classes: Insecta (order: bright colors (ie, clothing), and sweet odors (ie, Hymenoptera—bees, wasps, yellow jackets, and ants), perfumes, fragrances). Children commonly believe that and Arachnida (ticks, , and spiders). Virtually bees are aggressive , but they are mostly docile all possess some form of for immobi- creatures; indeed, the sometimes fearful behavior of lization and digestion of prey, yet only a select few species children around a nearby may increase the risk of a have developed venom delivery mechanisms capable of sting. Mass envenomations may occur when a hive is humans [2]. Pathophysiologic mechanisms of physically disturbed by children throwing rocks or other venom vary considerably among arthropods, and clinical objects at the hive [3]. immunologic considerations in the emergency depart- Bees exist in intricate colonies of thousands, with ment (ED) evaluation and treatment of these injuries are specific duties designated to various colony members to essential to patient management. protect the queen. Guard and soldier bees are tasked to defend the hive against trespassers (, humans, and Hymenoptera: Bees and Wasps Childrens Hospital Los Angeles, Los Angeles, CA. Bee and envenomations are the most widely USC/Keck School of Medicine, Los Angeles, CA. documented arthropod exposures, with 4081 pediatric California Poison Control System. exposures and 1 death reported to poison control centers Toxics Epidemiology Program, Los Angeles County Department of in 2005 [1]. Honeybees and are part of the Public Health, Los Angeles, CA. Reprint requests and correspondence: Cyrus Rangan, MD, FAAP, Apidae family. Yellow jackets, , and wasps are part ACMT, Los Angeles County Department of Public Health, 313 N of the Vespidae family. structure, behavior, and Figueroa Street, Room 127, Los Angeles, CA 90012. venom components differ between the 2 families; how- (E-mail: [email protected])

104 1522-8401/$ - see front matter ª 2007 Published by Elsevier Inc. doi:10.1016/j.cpem.2007.04.004 Immunologic and toxicologic considerations 105 other insects); however, less aggressive worker and the release of , leukotrienes, and other cyto- foraging bees may also sting when disturbed [4]. Yellow kines, manifesting with urticaria, dyspnea, hypotension, jackets and hornets may inflict solitary stings more bronchial constriction, and laryngeal edema [9]. The impulsively than the more docile honeybees, whereas allergenic properties of venom are similar to Africanized bees are often involved in mass envenoma- honeybee venom [10]. In mass envenomations, severe tions. The barbed surface of the honeybee causes reactions or death may occur from anaphylaxis or directly the insect to eviscerate itself as it attempts to fly away from toxic systemic effects of venom. after stinging, often leaving a detached stinger imbedded Wasp venom contains a number of neurotransmitters, at the site of injury. The venom sac may be visible at the neuromodulators, and immunomodulators, including proximal end of the stinger [5]. Bumblebees possess catecholamines, serotonin, tyramine, bradykinin, and slightly smoother and may be able to sting more mastoparans (histamine-releasing factors), all of which than once [5]. Wasp ( and yellow jacket) colonies induce pain and inflammation [11]. Wasp venom also are composed of a few hundred insects. These insects contains allergenic components, including phospholipase deliver venom via nonbarbed stingers, possess more A, phospholipase B, hyaluronidase, and antigen 5, which venom per sting than bees, and may attack singly or en mediate anaphylaxis and delayed hypersensitivity reac- masse [6]. Classically, a retained stinger in the tions [12]. indicates a bee sting, whereas the absence of a stinger on Honeybees, bumblebees, Africanized bees, and wasps visual inspection suggests envenomation by a wasp. universally cause painful burning papules at the site of However, bee stingers may extrude after stinging and envenomation, with progression to erythematous wheal- self-evisceration by honeybees, and bumblebees may and-flare reactions that begin to subside within 24 hours. escape without stinger detachment. Therefore, the Up to 50% of cases progress to larger edematous local absence of a stinger at the site of injury does not reactions that may mimic cellulitis or become vesicular or necessarily denote a wasp sting [6]. bullous [13]. Up to 5% of patients experience systemic A limited subset of the US population (1-2 people per reactions, including anaphylaxis. Symptoms of systemic 1000) is allergic or hypersensitive to bee or wasp stings, reactions may include nausea, vomiting, and dizziness in culminating in up to 50 deaths per year. Fatal reactions a dose-response fashion after multiple stings. Rarely do may occur in some patients without previous histories of these systemic reactions occur after solitary stings in the allergic sting reactions [7].Evaluationandtherapy absence of IgE-mediated anaphylaxis. Treatment of local depend upon the nature of the exposure (single vs mass reactions involves symptomatic local wound care with envenomation) and clinical severity. Bee venom can ice, cool compresses, and discretionary use of topical cause injury via immune-mediated mechanisms, includ- corticosteroids. Oral may decrease itching. ing local effects and anaphylaxis, or by systemic toxic Efficacy and safety of systemic administration of cortico- effects of venom in mass envenomations. Bee venom have not been validated in controlled trials [13] contains an aqueous solution of 4 primary components: but has been suggested in cases of severe swelling. mellitin, phospholipase A2, hyaluronidase, and mast-cell Imbedded stingers should be removed as early as degranulation protein [8]. Mellitin is the most abundant possible, mostly to alleviate pain but also to potentially component and mediates most of the local pain symp- prevent lingering envenomation. Despite anecdotal pre- toms. Mellitin also causes the formation of pores in red suppositions about various methods of proper stinger blood cell membranes. Phospholipase A2 subsequently removal in the ED setting, controlled trials demonstrate cleaves fatty acids from the lipid side of the cell that the rapid removal of retained stingers may be membranes, resulting in hemolysis. Clinically significant performed via any available method including tweezing, hemolysis occurs in few patients after bee stings. scraping with a credit card, or by applying and removing Hyaluronidase cleaves hyaluronic acid in connective adhesive tape [14]. tissue, allowing other venom components to travel easily Anaphylaxis must be treated promptly with epinephr- to nearby tissues. Mast-cell degranulation protein induces ine 0.01 mg/kg IM (1:1000 aqueous solution), repeated in histamine release from mast cells, resulting in inflamma- 10 to 15 minutes if clinical improvement is not apparent tion and local or systemic vasodilation [8]. Local dermal [9]. Standard treatments of other symptoms of anaphy- reactions typically consist of local edema and spongiosis, laxis, such as airway management, bronchodilators, endothelial cell hyperplasia, and necrosis. Lymphocytes, fluids, and pressors, are indicated based on symptoms. neutrophils, and eosinophils may infiltrate adjacent Signs and symptoms of anaphylaxis in bee envenomation perivascular and reticular tissues [8]. Immunoglobulin may be persistent or recrudescent. Therefore, clinical (Ig) E–mediated type I anaphylaxis, usually in response observation should take place for at least 6 hours after to phospholipase A2 or hyaluronidase, occurs independ- successful treatment. A short course of oral cortico- ently of the number of stings, but may complicate either steroids for 2 to 5 days is often used to prevent late-phase single stings or mass stingings. Cross-linking of IgE allergic reactions. Patients presenting with symptoms of antibodies attached to basophils and mast cells results in systemic IgE-mediated envenomation reactions should be 106 C. Rangan prescribed an epinephrine autoinjector. All patients with 50 bee stings should be observed for at least 24 hours in a a clinical history of anaphylaxis should be referred to an hospital setting [25-27].Fewdataareavailableto specialist for review of epinephrine autoinjector recommend clinical observation guidelines in mass wasp use, insect avoidance counseling, allergy testing, and stings; however, anecdotal evidence suggests careful potential evaluation for immunotherapy. Venom immu- observation in patients with more than 10 stings. notherapy has been shown to reduce the risk of systemic reactions in insect-sensitive patients with an efficacy of 95% to 97% [15]. Hymenoptera: Fire Ant Two species of imported fire ants, the black fire ant Hymenoptera: bbAfricanizedQ (Solenopsis invicta)andtheredfireant(Solenopsis Honeybees richteri), are poisonous to humans, in part due to their aggressive nature and propensity to attack in swarms. Fire In 1956, bee researchers brought African honeybees from ants are presumed to have entered the United States Africa into Brazil for their presumed aptitude for honey production. Although African bees were well suited to through the Port of Mobile, Alabama, in the 1930s via live in the Brazilian tropics, it was later determined that cargo ships’ soil ballast and are endemic to the southern these bees did not demonstrate superiority in honey states, eastern states, and in California [28]. One thousand production. African bees mated with the more docile ten pediatric exposures were reported to Poison Control European honeybees already present in North and South Centers in 2005, 812 of which occurred in children America, resulting in the aggressive hybrid bAfricanizedQ younger than 6 years [1]. Fire ant colonies are found in honeybee. Still a poor honey maker, Africanized honey- small, dome-shaped dirt mounds that may be easily bee colonies have been increasingly migrating through disturbed by children running, kicking, or jumping near North America every year [16]. Also referred to as bkiller the mounds. Several cases of swarming envenomations bees,Q Africanized honeybees attack in swarms, sting have occurred after children have disturbed the mound more readily, and have been described to chase fleeing with sticks. Children are encouraged to routinely wear victims [17].Althoughtheydonotflyfasterthan socks and long pants in endemic areas [29]. Hundreds of European honeybees, Africanized honeybees fly longer thousands of ants may inhabit a single colony, and mass distances, as much as 20 km [18]. Africanized honeybee stingings of several thousands of ants with little provoca- specimens are almost identical to honeybees in appear- tion are common. As a swarm of ants engulfs a child’s ance, and phenotypic distinction can only be made by extremity, chemical and vibrational signals transmitted trained entomologists. Mass envenomation with bee or throughout the colony apparently induce the ants to sting wasp stings presents with nausea, vomiting, diarrhea, almost simultaneously. Each ant grasps the victim’s skin lightheadedness, lethargy, edema, and seizures secondary with its mouthpiece and pivots on its jaw as it inflicts 6 to to histamine-mediated inflammation, hypotension, and 10 painful stings, over a few seconds, in a circular pattern direct toxic effects of venom components. These clinical via an abdominal stinger [30]. Upon close examination signs are not immune-mediated [19]. Hemolysis, rhab- the skin lesions appear as a ring of pinpoint pustules. This domyolysis, hemoglobinuria, and myoglobinuria may feature can help distinguish stings by solitary fire ants evolve over several hours to days after envenomation from injuries from other insects [31]. Stings progress to [20]. These laboratory parameters may be followed as wheals that evolve into pustules within 24 hours. crude indicators of systemic when they are noted In contrast to the venom of indigenous ants, fire ant to be abnormal; however, normal laboratory tests should venom does not contain formic acid. Instead, fire ant not be relied upon solely to assess patient disposition. venom contains an oily mixture of cytotoxic alkaloids, Acute tubular necrosis and oliguric renal failure can also resulting in painful, pruritic local skin lesions and develop and may necessitate dialysis [21,22]. Other systemic reactions such as edema [32]. A small fraction serum laboratory abnormalities may include elevated of fire contains aqueous alkaloids, including liver transaminases, elevated lactate dehydrogenase, and phospholipase, hyaluronidase, N-acetyl-b-glucosamini- decreased platelet counts [23].Massstingingsmay dase, and genus-specific antigens Sol i I, Sol i II, Sol i present with tens to thousands of stings (20-200 wasp III, and Sol i IV [33]. These antigens are responsible stings, 500-1000+ bee stings in case reports). Early for a 0.6% to 6% rate of IgE-mediated anaphylaxis to fatalities in mass Hymenoptera envenomations are likely fire ant stings [34]. Standard treatment for anaphylaxis secondary to anaphylaxis. On the other hand, dose- is recommended. Patients with mass envenomation response fatalities in mass envenomations tend to occur should be observed for several hours to monitor for several hours to days later, many with delayed onset of delayed symptoms or for recrudescence of systemic symptoms (up to 6-24 hours after the incident) [24]. toxic effects of venom. Supportive care, including cool Pediatric deaths have occurred with as few as 150 bee compresses, may relieve symptoms during the first stings and 30 wasp stings. All children with more than 24 hours. Severe itching may respond to oral antihist- Immunologic and toxicologic considerations 107 amines and topical corticosteroids. Topical application nomic relatives of the brown recluse do not cause of meat tenderizer has proved to have no therapeutic the same characteristic necrotic skin lesions. Therefore, value [35]. Pain from large single lesions has been clinicians in nonendemic states must consider an exten- treated with local injections of lidocaine in case sive differential diagnosisbeforecontemplatingthe reports, but this practice is not recommended for mass diagnosis of a brown recluse [38]. envenomations [6]. Brown recluse spider venom contains both cytotoxic and allergenic components, including alkaline phospha- tase, deoxyribonuclease, hyaluronidase, lipase, ribonu- Arachnida: Tarantulas clease, and sphingomyelinase D [39]. Sphingomyelinase Tarantulas are found in the arid regions of the United D is the most active component and is responsible for States. Tarantulas bite when aggravated but pose more regional skin necrosis and hemolysis. Sphingomyelinase danger from the trauma of the bite itself than from D is also responsible for a cascade of immune-inflam- envenomation in humans. Tarantula venom contains a matory reactions, beginning with the hydrolysis of number of polypeptides, including hyaluronidases, sphingomyelin into ceramide-1-phosphate. Ceramide-1- which cause local cytotoxicity and minor inflammation. phosphate induces the release of arachidonic acid from Occasionally, a histamine-mediated reaction develops, endothelial cells and promotes the synthesis and release but reports of anaphylaxis are extraordinarily rare. The of thromboxane, leukotrienes, and prostaglandins [40]. hairs on the back of the tarantula present a greater risk Neutrophils and complement infiltrate the site of to humans. When distressed, tarantulas rub their hind envenomation, leading to local ischemia, microvascular legs against the ventral surface of their to eject clotting and disintegration, destruction of skin tissue, the hairs on their backs. These hairs promote localized and subsequent necrosis [41]. The wound margin takes epidermal histamine-mediated reactions, manifesting several weeks to declare itself fully, and patients will with pain and urticaria. These injuries are particularly require regular follow-up with a plastic surgeon for prominent, however, when they occur in the eyes, wound care and eventual wound closure [42]. Immu- mouth, nose, oropharynx, or trachea. Supportive treat- nomodulatory therapy has not proved to be successful ment with cold compresses, analgesics, antihistamines, in the treatment of brown recluse spider envenomation. topical corticosteroids, and tetanus prophylaxis is rec- Early studies using dapsone to inhibit the infiltration of ommended for most contact reactions with tarantula neutrophils into the injury site did not demonstrate an hairs. Imbedded hairs may be removed from skin improvement in clinical outcome; indeed, recent studies surfaces by irrigation, tape removal, or tweezers. on the use of dapsone, triamcinolone, and diphenhydr- Ophthalmia nodosa, a granulomatous nodular reaction amine in necrotic lesions from brown recluse spider of the corneas, sclerae, and conjunctivae, may result envenomation have not demonstrated an improvement from contact of tarantula hairs with the eye. This in clinical outcome [43]. Hyperbaric oxygen therapy is condition requires immediate evaluation and treatment an unproven treatment modality [44].Antivenom by an ophthalmologist [36]. directed against sphingomyelinase D is not commercially available but is currently being investigated in exper- imental trials [45]. Arachnida: Brown Recluse Spider Arachnida: Black Widow Spider Envenomation by the brown recluse spider (Loxosceles In 2005, 551 pediatric cases of black widow spider reclusa), with the characteristic violin-shaped markings envenomation were reported to poison control centers on the dorsal aspect of its cephalothorax, is a subject of [1]. Widow spiders include the classic black widow tremendous controversy. In 2005, 464 cases of pediatric spider ( mactans) with a red hourglass pattern brown recluse spider bites were reported to poison on the underside of its shiny black abdomen, the western control centers [1]. Brown recluse spiders are endemic black widow spider (Latrodectus hesperus), northern to only a handful of central southern states but are widely black widow (Latrodectus variolus), southern brown perceived to live in other areas of the United States. widow (Latrodectus bishopi), and brown button spider Because the bite itself is usually painless, and because a (). Australia is the home of the red spider specimen is seldom seen or recovered around the back spider ( hasselti). Envenomation time of presumed exposure, brown recluse spider bites from these various Latrodectus species is similar, and have become a popular, although mostly inappropriate, cross-reactivity among venom and antivenom is well diagnosis of presumption for severe, solitary skin lesions documented [46]. Widow spider venom does not contain in many nonendemic states [37].Althoughsimilar allergenic components and clinical allergic reactions are spiders, such as Loxosceles deserta, pervade parts of extraordinarily rare. Instead, the chief pathogenic com- southern California, Nevada, and Arizona, these taxo- ponent of widow spider venom is a-, a neuro- 108 C. Rangan toxic polypeptide that binds to presynaptic nerve recep- [52]. Increased awareness of the nature and risk of tors at the neuromuscular junction and in the autonomic immune-mediated manifestations of Hymenoptera enve- , promoting the release of acetylcholine nomations and specialist referrals for appropriate into the synapse [47]. Although any muscle group may be patients may increase patient safety and prevent involved, the abdominal musculature is characteristically recurrent reactions. Awareness of the narrow prevalence affected with resultant severe pain and rigidity that may of brown recluse spider exposures and the extensive mimic an acute abdomen [48]. Other symptoms include differential diagnosis of necrotic skin lesions may save nausea, vomiting, agitation, and diaphoresis. Severe many patients from misdirected therapies [37]. Clinical hypertension occurs in 92% of cases, particularly in very familiarity with and suspicion of black widow enveno- young children [49]. Patients may experience some mations may encourage early consideration of immu- alleviation of pain and discomfort from opiates and notherapy with black widow spider antivenom, and benzodiazepines. Widow spider envenomations may prevent severe outcomes, especially in young children require intravenous immunotherapy (ie, antivenom) for in whom clinical history of black widow exposure may effective treatment. Antivenom is administered as an be difficult to determine [53]. intravenous injection of equine-derived IgG antibodies to widow spider venom. One to two vials are generally sufficient to corral the nanomolar concentrations of References circulating widow spider venom; however, additional 1. Lai MW, Klein-Schwartz W, Rodgers GC, et al. 2005 Annual report of the American Association of Poison Control Centers’ dosing may be necessary in patients who do not national poisoning and exposure database. Clin Toxicol 2006; demonstrate adequate recovery. Patients recover rela- 44:8032932. tively quickly, sometimes as soon as 15 minutes after 2. Yunginger JW. The sting—revisited. J Allergy Clin Immunol 1979; administration [50]. Antivenom should be considered in 64:122. any patient who does not respond to supportive treat- 3. Franca FO, Benvenuti LA, Fan HW, et al. Severe and fatal mass attacks by dkillerT bees (Africanized honey bees—Apis mellifera ment. Potential for severe allergic reactions (ie, anaphy- scutellata) in Brazil: clinicopathological studies with measurement laxis) to antivenom should not preclude the use of of serum venom concentrations. Q J Med 1994;87:269282. antivenom in severe cases. Clark et al described a 4. Breed MD, Guzman-Novoa E, Hunt GJ. Defensive behavior of honey retrospective case series of 163 cases of black widow bees: organization, genetics, and comparisons with other bees. Annu spider envenomations, 58 of whom were treated success- Rev Entomol 2004;49:271298. 5. Mulfinger L, Yunginger J, Styer W, et al. Sting morphology and fully with antivenom. Severe bronchospasm and death frequency of sting autotomy among medically important vespids occurred in one patient [51]. As with any equine-derived (Hymenoptera: Vespidae) and the (Hymenoptera: globulin, a skin test must be performed before admin- Apidae). J Med Entomol 1992;29:32528. istration. Patients with either documented horse dander 6. Fitzgerald KT, Flood AA. Hymenoptera stings. Clin Tech Small allergy or positive skin testing results have received black Anim Pract 2006;21:1942204. 7. Gelder C, Harris J, Williams D. Allergy to bee and wasp venom. widow spider antivenom without complications. Con- Br J Hosp Med 1996;55:349252. versely, patients without history of horse dander allergy 8. Hoffman DR, Shipman WH. Allergens in bee venom. I. Separation and with negative skin testing results have experienced and identification of the major allergens. J Allergy Clin Immunol anaphylaxis from the globulin components of the anti- 1976;58:551262. venom [50]. Clinicians must weigh the risks and benefits 9. Brown SG, Mullins RJ, Gold MS. Anaphylaxis: diagnosis and management. Med J Aust 2006;185:28329. of antivenom administration in patients with horse 10. Hoffman DR, Jacobson RS. Allergens in Hymenoptera venom. allergy and must monitor all patients undergoing anti- XXVII: bumblebee venom allergy and allergens. J Allergy Clin venom therapy for allergic reactions. Consultation with a Immunol 1996;97:812221. poison control expert may be warranted. Standard treat- 11. OwenMD,BridgesAR.Catecholaminesinhoneybee(Apismellifera L.) ment is recommended for anaphylaxis. and various vespid (Hymenoptera) venoms. Toxicon 1982;20: 1075284. 12. King TP, Spangfort MD. Structure and biology of stinging insect venom allergens. Int Arch Allergy Immunol 2000;123:992106. Practical Considerations 13. Wright DN, Lockey RF. Local reactions to stinging insects Although immunologic considerations regarding insect (Hymenoptera). Allergy Proc 1990;11:2328. envenomations are well documented, current practices 14. Visscher PK, Vetter RS, Camazine S, et al. Removing bee stings. Lancet 1996;348:30122. suggest that many patients with potential immune- 15. Moffitt JE, Golden DBK, Reisman RE, et al. Stinging insect mediated hypersensitivity from insect exposures do hypersensitivity: a practice parameter update. J Allergy Clin not receive appropriate follow-up: only approximately Immunol 2004;114:869296. 50% of patients with severe reactions receive a 16. Kim KT, Oguro J. Update on the status of Africanized honey bees in prescription for a rapid epinephrine autoinjector, fewer the western states. West J Med 1999;170:22022. 17. Guzman-Novoa E, Hunt GJ, Uribe JL, et al. Confirmation of QTL than 12% of patients received educational information effects and evidence of genetic dominance of honeybee defensive regarding insect avoidance, and slightly more than one behavior: results of colony and individual behavioral assays. Behav third of patients were referred to an allergy specialist Genet 2002;32:952102. Immunologic and toxicologic considerations 109

18. Breed MD, Guzman-Novoa E, Hunt GJ. Defensive behavior of honey their known distributions but are perceived to exist throughout the bees: organization, genetics, and comparisons with other bees. Annu United States. J Med Entomol 2005;42:512221. Rev Entomol 2004;49:271298. 38. Swanson DL, Vetter RS. Bites of brown recluse spiders and 19. Vetter RS, Visscher PK, Camazine S. Mass envenomations by honey suspected necrotic arachnidism. N Engl J Med 2005;352:70027. bees and wasps. West J Med 1999;170:22327. 39. Rekow MA, Civello DJ, Geren CR. Enzymatic and hemolytic 20. Betten DP, Richardson WH, Tong TC, et al. Massive honey bee properties of brown recluse spider (Loxosceles reclusa) and envenomation-induced rhabdomyolysis in an adolescent. Pediatrics extracts of venom apparatus, cephalothorax and abdomen. Toxicon 2006;117:23125. 1983;21:44124. 21. Grisotto LS, Mendes GE, Castro I, et al. Mechanisms of bee venom- 40. Pettus BJ, Bielawska A, Spiegel S, et al. Ceramide kinase mediates induced acute renal failure. Toxicon 2006;48:44254. cytokine- and calcium ionophore-induced arachidonic acid release. 22. Mejia G, Arbelaez M, Henao JE, et al. Acute renal failure due to J Biol Chem 2003;278:38206213. multiple stings by Africanized bees. Ann Intern Med 1986;104: 41. Tambourgi DV, Paixao-Cavalcante D, Goncalves de Andrade RM, et 21021. al. Loxosceles sphingomyelinase induces complement-dependent 23. Kini PG, Baliga M, Bhaskaranand N. Severe derangement of the dermonecrosis, neutrophil infiltration, and endogenous gelatinase coagulation profile following multiple bee stings in a 2-year-old boy. expression. J Invest Dermatol 2005;124:725231. Ann Trop Paediatr 1994;14:15325. 42. Swanson DL, Vetter RS. . Clin Dermatol 2006; 24. Schumacher MJ, Schmidt JO, Egen NB. Lethality of dkillerT bee 24:213221. stings. Nature 1989;337:413. 43. Elston DM, Miller SD, Young III RJ, et al. Comparison of colchicine, 25. Sherman RA. What physicians should know about Africanized dapsone, triamcinolone, and diphenhydramine therapy for the honeybees. West J Med 1995;163:54126. treatment of brown recluse spider envenomation: a double-blind, 26. Schumacher MJ, Egen NB. Significance of Africanized bees for controlled study in a rabbit model. Arch Dermatol 2005;141:59527. public health. Arch Intern Med 1995;155:2038243. 44. Phillips S, Kohn M, Baker D, et al. Therapy of brown spider 27. Tunget CL, Clark RF. Invasion of the dkillerT bees. Separating fact envenomation: a controlled trial of hyperbaric oxygen, dapsone, and from fiction. Postgrad Med 1993;94:9224. cyproheptadine. Ann Emerg Med 1995;25:36328. 28. Ginsburg CM. Fire ant envenomation in children. Pediatrics 45. Olvera A, Ramos-Cerrillo B, Estevez J, et al. North and South 1984;73:689292. American Loxosceles spiders: development of a polyvalent anti- 29. Goddard J. Personal protection measures against fire ant attacks. venom with recombinant sphingomyelinases D as antigens. Toxicon Ann Allergy Asthma Immunol 2005;95:34429. 2006;48:64274. 30. Cohen PR. Imported fire ant stings: clinical manifestations and 46. Daly FF, Hill RE, Bogdan GM, et al. Neutralization of Latrodectus treatment. Pediatr Dermatol 1992;9:4428. mactans and L. hesperus venom by redback spider (L. hasseltii) 31. deShazo RD, Butcher BT, Banks WA. Reactions to the stings of the antivenom. J Toxicol Clin Toxicol 2001;39:119223. imported fire ant. N Engl J Med 1990;323:46226. 47. Grishin E. Polypeptide neurotoxins from spider venoms. Eur J 32. Nguyen SA, Napoli DC. Natural history of large local and Biochem 1999;264:276280. generalized cutaneous reactions to imported fire ant stings in 48. Rauber A. Black widow spider bites. J Toxicol Clin Toxicol 1983- children. Ann Allergy Asthma Immunol 2005;94:387290. 1984;21:473285. 33. Hoffman DR. Allergens in Hymenoptera venom XXIV: the 49. Woestman R, Perkin R, VanStralen D. The black widow: is she amino acid sequences of imported fire ant venom allergens deadly to children? Pediatr Emerg Care 1996;12:36024. Sol i II, Sol i III, and Sol i IV. J Allergy Clin Immunol 1993; 50. Clark RF. The safety and efficacy of antivenin Latrodectus mactans. 91(Pt 1):7128. J Toxicol Clin Toxicol 2001;39:12527. 34. Stafford CT. Hypersensitivity to fire ant venom. Ann Allergy Asthma 51. Clark RF, Wethern-Kestner S, Vance MV, et al. Clinical Immunol 1996;77:87295. presentation and treatment of black widow spider envenomation: 35. Ross Jr EV, Badame AJ, Dale SE. Meat tenderizer in the acute treatment a review of 163 cases. Ann Emerg Med 1992;21:78227. of imported fire ant stings. J Am Acad Dermatol 1987;16:1189292. 52. Johnson T, Dietrich J, Hagan L. Management of stinging insect 36. Choi JT, Rauf A. Ophthalmia nodosa secondary to tarantula hairs. hypersensitivity: a 5-year retrospective medical record review. Ann Eye 2003;17:43324. Allergy Asthma Immunol 2006;97:22325. 37. Vetter RS. submitted as suspected brown recluse spiders 53. Miller TA. : bite of the black widow spider. Am Fam (Araneae: Sicariidae): Loxosceles spiders are virtually restricted to Phys 1992;45:18127.