Bites that poison: A tale of spiders, snakes, and scorpions

By Bruce E. Herman, MD, and Elisabeth Guenther Skokan, MD, MPH

Snake and spider bites occur frequently, but envenomations are rare. It's important to know when a bite is potentially serious. Here's how to recognize the signs and intervene appropriately.

I don't like spiders and snakes," the old Jim Stafford tune begins, and the song reflects our visceral fear and loathing of creepy crawlers. As it turns outs, this fear is largely unwarranted. While some 50,000 pediatric bites and stings were reported to poison control centers in 1997, only a handful of cases ended in death or serious illness.¹ Nevertheless, people still react dramatically to the news of a snake or spider bite and their reactions are often reinforced by needlessly aggressive treatment.

The fact is, envenomations are rare, presentations vary in severity, and treatment recommendations are often based on speculation and anecdote rather than scientific evidence. With the facts provided here, pediatricians will be better able to tell potentially serious bites from ones that need little more than a cold compress, and to intervene effectively when bites require immediate treatment.

Spiders

There are over 20,000 species of venomous spiders. Almost all spiders have poison glands that deliver venom through their chelicerae or fangs. However, only approximately 50 species of spiders have chelicerae large and strong enough to penetrate the human dermis. In the United States, only black widow spiders and brown recluse spiders are known to cause significant envenomations. In 1997 these two spiders accounted for 4,771 envenomations, or 5% of all bites and stings reported to the American Association of Poison Control Centers.¹

Spider bites are difficult to diagnose because the offending creature is rarely available. The initial symptoms may be so mild as to go unnoticed or the spider is crushed beyond recognition. Knowledge of spiders indigenous to your area is important. Because of the potential of adverse reactions, especially in the very young, advise families to get medical care after any known or suspected black widow or brown recluse spider bites.

Black widow spiders. These creatures belong to the genus Latrodectus. Loosely translated from Greek, Latrodectus mactans, the species found most commonly in North America, means "murderer."² The black widow spider received its name because it was thought that the female ate the male after mating. The female is dangerous not only to her mate but to humans as well. The mature female is roughly the size of a quarter, jet black, with an hourglass-shaped red mark on the underside of her abdomen. The male is one third the size of the female, and his fangs are not big enough for human envenomation (Figure 1). Black widow spiders inhabit every state but Alaska and are most commonly found in the South, Ohio Valley, Southwest, and West Coast. They live beneath shelves and in attics, barns, trash piles, garages, and other dimly lighted areas that would attract flies. Earlier this century most bites occurred around the genitals while people were using the outhouse.² With the advent of indoor plumbing, envenomations have become less frequent and generally occur when the web is disturbed or the spider is trapped against the skin. Bites are more frequent in the warm months, when spiders are more active.

Black widow spider envenomation (BWSE) has been thought to be dangerous and even deadly, especially in children. However, there have been no reported pediatric deaths since 1958.¹

BWSE causes a constellation of findings, both local and systemic, that are usually self-limited. The bite may be painless or cause a pinching or pinprick sensation. In up to two thirds of children with BWSE, a "target" lesion consisting of an erythematous ring around a pale center is identified at the bite site.³ This lesion develops within one to two hours and is specific for BWSE, but it usually fades within 12 hours and is often missed.⁴

Systemic findings result from alpha-latrotoxin, the potent neurotoxin found in the venom. More powerful than rattlesnake venom, it causes release and subsequent inhibition of reuptake of acetylcholine and norepinephrine, leading to overstimulation of the motor end plate. This results in hallmark symptoms of muscle pain and cramping in the large muscle groups (abdomen, back, and thighs). Abdominal pain and rigidity are the most common findings in children regardless of bite location.³ These symptoms usually begin within 30 to 90 minutes of envenomation and peak in three to 12 hours. Anxiety characterized by irritability and agitation is often seen in children, especially those too young to talk. Muscle weakness and refusal to walk or bear weight are other common findings. Expiratory grunting and respiratory distress may be present, with chest or abdominal pain. Severe hypertension is extremely common but almost always asymptomatic.³ Less common findings include tremors, paresthesias, tetany, facial grimacing, periorbital edema, and headache (Figure 2). Cholinergic symptoms such as flushing, nausea, vomiting, salivation, bronchorrhea, and diaphoresis may also be present. The diaphoresis may be generalized, at the bite site, or in unusual locations distant from the bite site such as on the face, nose, or feet.^5,6

Symptoms generally wax and wane, gradually diminishing over 12 to 72 hours. However, some of those bitten may describe paresthesias, muscle aches, weakness, malaise, and fatigue for days or weeks.⁴

The diagnosis of BWSE is challenging, as the child is often unaware of the envenomation or unable to describe the symptoms. Since unexplained irritability can be the chief symptom, it is easy to understand the difficulty of the differential diagnosis. Apart from the classic "target" lesion, local symptoms are difficult to differentiate from other spider or insect bites (Figure 3).

Differentiating BWSE from an acute surgical abdomen is the usual dilemma. Unlike the child with peritonitis or appendicitis, the child bitten by a black widow has no peritoneal signs, and pain from BWSE is usually more generalized, involving muscle groups other than the abdomen. The patient with BWSE is constantly moving around seeking a comfortable position, while a child with an acute abdomen avoids movement. The differential diagnosis also includes renal colic, opioid withdrawal, organophosphate poisoning, and tetanus.²

The treatment of BWSE is controversial. A grading scale to characterize the severity of BWSE appears in the table and can be used to guide therapy.

Initial therapy is to stabilize the patient's airway, breathing, and circulation (ABCs); monitor vital signs, especially blood pressure, and respiratory status; and give vigorous wound care. The wound should be cleansed thoroughly with soap, water, or chlorhexidine gluconate (Hibiclens). The patient's tetanus status should be updated. Give a tetanus booster if the patient has not had scheduled immunizations, or if the patient is unsure about his status. The patient or parent should be advised to use rest, immobilization, cold compresses or ice, and elevation therapy (known as RICE). Prophylactic antibiotics are not needed. Oral analgesics (acetaminophen, ibuprofen, or codeine) may provide sufficient relief for mild (Grade 1) envenomations. Symptoms associated with BWSE generally peak within three to four hours. Children who have not developed symptoms in that time or children whose symptoms are controlled with oral medications do not need hospitalization and can be safely sent home from the office or emergency department with close follow-up. Tell the parents to bring the child back if pain increases or is not controlled with oral medications.

Treatment of more severe envenomations (Grade 2 or 3) centers on relief of muscle cramping and pain. Intravenous (IV) access is recommended, to facilitate administration of medications and avoid the pain of intramuscular injections. Most Grade 2 and 3 envenomations can be conservatively managed with parenteral opioids, alone or in combination with benzodiazepines.⁶ Morphine alone (0.1 to 0.2 mg/kg IV every two to four hours) or meperidine (1 to 1.5 mg/kg IV every three to four hours) may be sufficient to control pain. If necessary for muscle relaxation or to relieve anxiety, add a benzodiazepine such as diazepam (0.1 to 0.2 mg/kg IV every two to four hours) or lorazepam (0.05 to 0.1 mg/kg IV every four to eight hours).

Calcium gluconate, though advocated for BWSE for decades, has not been shown to provide consistent or sustained relief. In one series, it was ineffective in 96% of BWSE.⁶ Other muscle relaxants such as methocarbamol or dantrolene sodium have proved even less effective than calcium salts.⁷ We don't recommend the routine use of these medications in treating BWSE.

The use of Latrodectus antivenin remains controversial. Derived from horse serum, it has been shown to provide rapid and lasting relief of symptoms, even when given as long as 36 to 90 hours after the bite.^8­10 One 2.5 mL vial, diluted in 50 mL to 100 mL saline or D5W and given slowly over 30 to 60 minutes, is usually sufficient.

Concerns about anaphylaxis and serum sickness limit the routine use of antivenin. More deaths have been reported from the use of antivenin than from BWSE. Although skin testing should be performed prior to its use, anaphylaxis has been seen in up to 9% of patients after a negative skin test and 80% after a positive test.² Premedication with antihistamines may help, but be prepared to treat anaphylaxis. Serum sickness may occur one to four weeks after antivenin use, and can be treated with analgesics, antipyretics, antihistamines, or steroids.

Parenteral opioids alone or with benzodiazepines are the first line of therapy for serious BWSE, in addition to supportive care such as IV hydration. If repeated doses of medications are required to control symptoms, admit the child to the hospital. Children whose symptoms are resistant to conservative management (for example, if pain is unresponsive to parenteral opioids and benzodiazepines) or persist beyond 12 hours should be considered for antivenin.

Brown recluse spiders. There are 12 species of brown recluse spiders native to North America; the most common is Loxosceles reclusa. These small (6 mm to 15 mm long and 4 mm to 6 mm wide), fawn to brown spiders are often called "violin" or "fiddleback" spiders because of the brown or yellow violin shaped marking on their dorsal cephalothorax (Figure 4). They are found throughout the United States, most commonly in the South and midwestern states. These spiders are nocturnal hunters that prefer dark, warm, dry, protected areas such as woodpiles, closets, storage boxes, and garages.¹¹ Envenomations occur most frequently in the spring and summer months, often when a spider is trapped against the skin.

Brown recluse venom contains several proteolytic enzymes used to digest the spider's prey, with sphingomyelinase D the major cytotoxic factor. Envenomations take a clinical course that varies from mild local irritation to large necrotic skin lesions and systemic effects. Ninety percent of bites go unnoticed or cause only mild, transient burning or a small erythematous papule that heals quickly.⁸ In the few that have more severe symptoms, initial local itching and burning progress to an erythematous blister within two to eight hours. Over the next 24 to 72 hours, there is intense local vasospasm and inflammation as the blister evolves into a red, white, and blue lesion. The central bleb develops into a deep necrotic ulcer of variable size (1 cm to 30 cm in diameter), which heals over several weeks to months. Envenomations in fatty areas such as the abdomen, thighs, and buttocks form more extensive necrosis because of the tenuous blood supply in these regions.

Systemic symptoms develop in approximately 40% of envenomations, usually within 12 to 72 hours. Symptoms are generally proportionate to the amount of venom injected. Flu-like symptoms such as fever, malaise, arthralgias, headache, nausea, and vomiting are seen, often in conjunction with a scarlatiniform rash. Systemic loxoscelism is a rare systemic reaction seen almost exclusively in children and characterized by hemolysis, thrombocytopenia, hemorrhage, shock, and renal failure.

Treatment is mainly supportive and includes RICE therapy (sphingomyelinase D is more active at increased temperatures), analgesics, tetanus update, and vigorous wound care. Consider consultation with a plastic surgeon on wounds that are large, disfiguring, or in a location that may compromise function.⁴ Perform screening tests for hemolysis, including a complete blood count and urinalysis. Antibiotics are not indicated for prophylaxis but may be used for evidence of infection.

Several treatments have been advocated to decrease venom spread and local inflammation, including local and systemic steroids, vasodilators, and early surgical incision. None has been shown to aid healing, and some may make things worse. Dapsone has been thought to decrease inflammation and necrosis by inhibiting polymorphonuclear chemotaxis,¹¹ and hyperbaric oxygen therapy may increase neovascularization. Neither has achieved consistent beneficial effects in animal trials,^11­14 however, and no human trials have been performed. Since brown recluse envenomations rarely have serious complications and the vast majority of people bitten do well with supportive care, aggressive medical therapy does not appear warranted at this time.^{15, 16}

Snakes

There are over 7,000 venomous snakebites in the United States annually, about half of them in children.⁷ Pit vipers (Crotalidae family), including rattlesnakes, cottonmouths, and copperheads, account for over 95% of snakebites.⁴ Pit vipers have triangular heads, elliptical pupils, hinged fangs connected to venom glands, and a heat-sensing "pit" between their nostril and eye that lets them locate and track their prey. These snakes are found throughout the continental United States except for Maine and Washington, DC. Most bites occur in the Southeast and Southwest during the warm months when snakes are more active, peaking in July and August. Children are usually bitten on the leg or foot (Figure 5), while adolescents are more commonly bitten on hand or arm while teasing or trying to handle the snake.¹⁸ Children have smaller extremities, less subcutaneous tissue, and receive a larger dose of venom per kilogram than adults, so their clinical course is often more severe. Snakes can control how much venom they inject, and symptoms range from little or no reaction (dry bites) to marked tissue necrosis and edema with severe systemic effects. Fortunately, death is rare.

Venoms help snakes immobilize and digest their prey. In humans, these enzymes cause local tissue degradation, capillary leakage, hemolysis, coagulopathy, and neurotoxicity.

The classic early signs and symptoms of snake envenomation are pain, edema, and redness or bruising around the bite, usually appearing within 30 minutes, sometimes taking longer in children. As the venom spreads, erythema and edema progress for up to 24 hours. Local areas may become extremely swollen and tense, although true compartment syndrome is rare, as most snakebites involve subcutaneous tissues. Blebs and bullae may develop from local tissue degradation (Figure 6), and evolve into areas of necrosis. Systemic effects may rapidly follow local effects, be delayed, or appear without local symptoms. They may include nausea, vomiting, a metallic taste in the mouth, a tingling sensation, muscle twitching, and in severe envenomations, coagulopathies, hypotension, and shock. Although laboratory coagulopathies may be severe, true disseminated intravascular coagulation (DIC) and clinical bleeding are rare.

Initial first aid therapies are controversial, but transport to the nearest medical facility as soon as possible is very important. The key to a successful outcome is early diagnosis and treatment The best snakebite kit is the key to a car that runs! Reassurance, immobilization, and removal of rings or constricting items should be done in the field.

Traditional interventions such as tourniquets, electric shock therapy, cryotherapy, and attempts at venom removal should be strongly discouraged. These have questionable efficacy and may significantly increase morbidity for a number of reasons.¹⁷ Tourniquets can cut off a patient's blood supply, leading to amputation, while electric shock can cause electrocution; cryotherapy can cause tissue necrosis; and an incision aimed at venom removal can cause tendon, vessel, and nerve damage while suction by mouth may contaminate the wound. Loose-fitting constriction bands may be used when a treatment delay of two or more hours is anticipated.¹⁸

Successful hospital treatment is based on attention to the ABCs, vigorous fluid resuscitation, analgesia, laboratory evaluation, and the early use of antivenin. Laboratory evaluation should include a complete blood count, type and crossmatch for blood products, coagulation studies and DIC screen, blood urea nitrogen (BUN), creatinine, urinalysis, and creatine phosphokinase (CPK). Measuring the circumference of the affected arm or leg every 20 to 30 minutes will track progression of the injury as well as efficacy of treatment. Wound care should consist of local cleansing and tetanus update. Prophylactic antibiotics are probably not indicated, as the incidence of wound infection is very low.¹⁹

Antivenin therapy is the mainstay of treatment and should be used for rapid progression of swelling or the presence of coagulopathy, shock, neurologic symptoms, or other systemic symptoms of a severe envenomation. The antivenin is a hyperimmune horse serum product that neutralizes the venom of all North American Crotalidae snakes. It works best if given within four to six hours of a bite, is less effective after 12 hours, but should be used up to 24 to 48 hours after the bite if coagulopathies or bleeding are present. Because of its source, horse serum, antivenin can cause anaphylaxis or delayed serum sickness reactions. Skin testing should be done on those who are to receive antivenin, but results should be interpreted with caution as there are many false-positive and false-negative reactions.¹⁸ If antivenin is used, dilute five vials in 250 mL of saline and give over one to two hours, cautiously increasing the infusion rate as tolerated. If swelling continues or there are coagulation defects, five more vials should be given in a similar manner. Repeat these steps until there is no change in serial circumferential measurements and coagulation defects have reversed (Figure 7). Be prepared to treat anaphylaxis, and treat milder reactions with antihistamines. A delayed serum sickness may occur five to 14 days after antivenin use and is likely to be proportional to the amount of antivenin used. It can be treated with a short course of steroids and antihistamines.

Adjunctive therapy is controversial and not usually necessary. Blood products should be used only with clinical bleeding, not for laboratory abnormalities, since these generally reflect inadequate antivenin use. Steroids are not indicated for acute management but may be used with delayed reactions. Be cautious about surgical interventions. Fasciotomy for compartment syndrome is indicated only for documented elevation of intracompartmental pressures; early surgical excision to reduce venom load should be avoided; and surgical debridement of a necrotic lesion should be delayed until it is well demarcated.^17,18

Because of the risks associated with antivenin of equine origin, an antivenin derived from sheep serum has been developed for use against envenomations by North American crotalids. Early reports have shown it to be effective and safe, with minimal allergic reactions.^20,21 It may replace the current product and make it easier to treat envenomations with antivenin.

Although up to 25% of snakebites are "dry bites,"¹⁸ many authors recommend admitting all children with venomous snakebites for observation because of the risks of delayed symptoms.^7,22 All children who require antivenin should be monitored in an intensive care setting.

Education concerning preventive measures should include wearing protective clothing, not reaching into areas where snakes may hide, and avoiding provocative behavior around snakes. Your regional poison control center can be a valuable resource in treating snake envenomations.

Scorpions

The southwestern desert scorpion (Centruroides exilicaida) is the only scorpion species of medical importance in the United States. Also known as the Arizona bark scorpion, it is found mainly in Arizona but also in Texas and California. Yellow or brown in color and approximately 5 cm in length, these scorpions look like the land cousin of the shrimp. They have a pair of anterior pincers and a moderately long, extremely mobile tail with a stinger on the end (Figure 8). They usually reside upside down in brush and trees, and most envenomations occur at night when they are more active. Children are stung most commonly on their extremities.²³

Most victims suffer only local pain, tenderness, and tingling that may begin immediately and peak in about five hours. Children often have more severe symptoms than adults do, and although no deaths have been reported in over 30 years, significant complications can occur.⁷ Bark scorpion venom is mainly neurotoxic. It overstimulates the sympathetic and parasympathetic nervous system, causing increased temperature, tachycardia or bradycardia, dysrhythmias, hypertension, agitation, and increased secretions. Cranial nerve dysfunction may cause rapid disconjugate eye movements, contractions of muscles in the tongue and face, and loss of pharyngeal muscle tone. Peripheral motor neuron manifestations include muscle contractions and uncontrolled jerking of the extremities. This constellation of symptoms may be mistaken for a seizure.⁴ Increased secretions, loss of pharyngeal tone, and uncoordinated contraction of respiratory muscles may lead to respiratory distress.

Treatment of scorpion envenomation is primarily supportive care with special attention to airway control. Wound care includes local cleansing and tetanus update. Children with systemic symptoms should be admitted and closely monitored. Analgesia and sedation relieve pain and agitation. Monitor the airway closely when using opioids and benzodiazepines because of their respiratory effects. Intravenous beta blockers have been used for extreme tachycardia and severe hypertension.²⁴

A hyperimmune goat serum antivenin has been shown to be effective in relieving life-threatening symptoms associated with severe envenomations in children,²⁵ but it is only available in Arizona (Arizona Poison Control Center, 602-253-3334).

Hymenoptera

Insect stings account for approximately one third of all envenomations. They cause approximately 40 to 150 deaths each year; less than 10% of these victims are children. Fatalities are not a direct consequence of the venom but result from sensitization of the sting victim and subsequent anaphylaxis. Honeybees (Apis mellifera) are generally mild-mannered and sting defensively. Only female bees can sting, as the stinger is a modified ovipositor ("egg layer"). The stinger is barbed and remains in the skin, eviscerating and killing the species bee after the sting; therefore, the bee sting is in effect a kamikaze mission. Vespid species include yellowjackets, hornets, and wasps. They are carnivores and sting to obtain prey. Vespids are generally more aggressive than bees and their stingers are smooth, allowing them to sting many times.

Hymenoptera venoms contain enzymes that directly affect vascular tone and permeability. More important, they contain protein antigens that are immunogenic and sensitize the victim for later IgE­mediated anaphylactic reactions. There is little cross reactivity between apid and vespid venoms.²⁶ As a result, a sting from a honeybee would not sensitize an individual to wasps or result in an anaphylactic reaction after a subsequent wasp sting.

Clinical manifestations of hymenoptera envenomation are generally local and reflect the vasoactive affects of the venom. Most are mild, with local pain, erythema, and edema. Large (greater than 5 cm in diameter) local reactions occur in approximately 10% of stings. They may involve an entire extremity and last for days. Sometimes confused with cellulitis, the symptoms of envenomation have a more abrupt onset, usually appearing within six to 24 hours of the sting.

Treatment of hymenoptera envenomation is symptomatic: cold compresses, analgesics, and an antihistamine. Large local reactions may benefit from a short course of steroids and antihistamines.

Up to 4% of the population is sensitized to bee stings, and systemic IgE­mediated reactions occur in approximately 1% of bee stings. In children, 70% of these cause nonlife-threatening cutaneous symptoms such as generalized urticaria, flushing, pruritus, or angioedema. Although rare, true anaphylaxis is a medical emergency and should be treated as such. Epinephrine is the mainstay of treatment. For details, see "Taking action against anaphylaxis" in the August issue of Contemporary Pediatrics.

Prevention of anaphylaxis includes patient education about ways to avoid these creatures, emergency treatment kits containing epinephrine and an antihistamine, and possibly venom immunotherapy. It is difficult to identify the children who should receive venom immunotherapy; 50% of those who die of anaphylaxis after a sting have no previous history of systemic reactions to bee stings.²⁶

African killer bees

African "killer" bees (Apis mellifera scutellata) are examples of a genetic experiment gone bad. They were imported into Brazil in 1956 to increase honey production. However, 26 queen bees escaped in 1957. They spread northward through Central America and were first discovered in the United States in Texas in 1990. They have since been found in Arizona and southern California. Their spread is thought to be temperature-limited.²⁷ They are quite aggressive and sting in huge swarms, sometimes giving hundreds or even thousands of stings.

Local and anaphylactic reactions to killer bee stings are similar to those of honeybees. However, systemic anaphylactoid reactions and even fatalities can result from the toxic amounts of foreign protein (venom) injected.^28­30 Symptoms may resemble those of anaphylaxis reactions, but may also include rhabdomyolysis, hemolysis, hypotension, shock, and renal failure. Treatment of these systemic reactions is the same as for anaphylaxis.

Fire ants

Fire ants were imported into Mobile, AL, aboard ships from South America in the early 1900s. The red fire ant (Solenopsis invicta) has become the predominant species and spread throughout the southeastern United States and as far northwest as Oklahoma³¹ (Figure 9). Although their range is thought to be limited by average minimum temperature (10° F), it is estimated they will soon occupy over one quarter of the land area of the United States, from Virginia to California. They live in large mounds in open fields, playgrounds, and yards. They are social, aggressive insects with no natural enemy and tend to attack in swarms. Multiple stings are the norm. Stings are more common in children, occurring most frequently in the summer on the feet and legs. In endemic areas, up to 60% of the population is stung by fire ants each year.

Fire ant venom contains toxic alkaloids that produce a sharp burning sensation (hence the name). It also contains a small protein fraction that can sensitize the victim for subsequent systemic and anaphylactic reactions. Anaphylaxis has been estimated to occur in 0.6% to 4% of stings, commonly in children.

Clinical manifestations are mainly local dermatologic reactions. An initial wheal and flare reaction evolves within 24 hours into a highly pruritic sterile pustule that sloughs off in two to three days. Large local reactions develop in 17% to 56% of envenomations.³¹ These may involve an entire extremity and are characterized by erythema, edema, induration, and pruritus. They last one to three days.

Treatment of stings is local and symptomatic. Frequent cleansing of the affected areas is essential to prevent secondary infection. Antihistamines or topical anesthetic creams may help. Although topical steroids have not been shown to be effective for local reactions, a short course of systemic steroids may help for a large local reaction. Systemic reactions and anaphylaxis should be treated as discussed above.

Immunotherapy with whole-body extracts, though not consistently effective, should be considered for those patients who live in infested areas and are known to be sensitized.

Distilling the message

Snake and spider bites are frightening but envenomations are rare. Pediatricians need to be able to separate serious bites that require immediate hospitalization from those that can be treated simply at home. Education concerning precautionary measures can help patients avoid bites if they live in areas attractive to these creepy creatures.

DR. HERMAN is Assistant Professor, Pediatric Emergency Medicine, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT.

DR. SKOKAN is Fellow, Pediatric Emergency Medicine, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT.

REFERENCES

1. Litovitz TL, Klein-Schwartz WK, Dyer KS, et al: 1997: Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 1998:16:443

2. Mack RB: Will the defendant please rise? Black widow spider poisoning. NC Med J 1994:55:86

3. Woestman R, Perkin R, Van Stralen D: The black widow: Is she deadly? Pediatr Emerg Care 1996;12:360

4. Bond GR: Snake, spider, and scorpion envenomations in North America. Pediatr Rev 1999:20:147

5. Banner W: Bites and stings in the pediatric patient. Curr Probl Pediatr 1988;1:9

6. Clark RF, Wethern-Kestner S, Vance MV, et al: Clinical Presentation and treatment of black widow envenomation: A review of 163 cases. Ann Emerg Med 1992;21:782

7. Bush SP, Thomas TL, Chin ES: Envenomations in children. Pediatr Emerg Med Reports 1997;2:1

8. Suntorntham S, Roberts JR, Nilsen GJ: Dramatic clinical response to the delayed administration of black widow spider antivenin. Ann Emerg Med 1994;24:1198

9. Allen RC, Norris R: Delayed use of widow spider antivenin. Ann Emerg Med 1995;26:393

10. O'Malley GF, Dart RC, Kuffner EF: Successful treatment of latrodectism with antivenin after 90 hours. N Engl J Med 1999;340:657

11. Barrett SM, Romine-Jenkins M, Fisher DE: Dapsone or electric shock therapy of brown recluse spider envenomation? Ann Emerg Med 1994; 24:21

12. Phillips S, Kohn M, Baker D, et al: Therapy of brown spider envenomation: A controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine. Ann Emerg Med 1995; 25:363

13. Hobbs GD, Anderson AR, Greene TJ, et al: Comparison of hyperbaric oxygen and dapsone therapy for Loxosceles envenomation. Acad Emerg Med 1996;3:758

14. Maynor ML, Moon RE, Klitzman B, et al: Brown recluse spider envenomation: A prospective trial of hyperbaric oxygen therapy. Acad Emerg Med 1997;4:184.

15. Hobbs GD: Brown recluse spider envenomation: Is hyperbaric oxygen the answer? Acad Emerg Med 1997;4:165

16. Wright SW, Wrenn KD, Murray L, et al: Clinical presentation and outcome of brown recluse spider bite. Ann Emerg Med 1997;30:28.

17. Holstege CP, Miller MB, Wermuth M, et al: Crotalid snake envenomation. Crit Care Clin 1997;13;889

18. Gold BS, Wingert WA: Snake venom poisoning in the United States: A review of therapeutic practice. South Med J 1994; 87:579

19. Kerrigan KR, Mertz BL, Nelson SJ, et al: Antibiotic prophylaxis for pit viper envenomation. World J Surg 1997;21:369

20. Clark RF, Williams SR, Nordt SP, et al: Successful treatment of Crotalid-induced neurotoxicity with a new polyspecific Crotalid Fab antivenom. Ann Emerg Med 1997;30:54

21. Dart RC, Seifert SA, Carroll L, et al: Affinity-purified, mixed, monospecific Crotalid antivenom ovine Fab for the treatment of Crotalid venom poisoning. Ann Emerg Med 1997; 30:33

22. Guisto JA: Severe toxicity from Crotalid envenomation after early resolution of symptoms. Ann Emerg Med 1995;26:387

23. Thomas R, Stevens K, Penix J, et al: Descriptive study of demographics of scorpion sting patients. J Toxicol Clin Toxicol 1997;35:529

24. Herman BE, Erickson T, Bowman MJA: Spider bites, in Strange GR, Ahrens WR, Lelyveld S et al (eds), Pediatric Emergency Medicine: A Comprehensive Study Guide. New York, McGraw-Hill, 1996

25. Holve S: Treatment of snake, insect, scorpion, and spider bites in the pediatric emergency department. Curr Opin Pediatr 1996;8:256

26. Valentine MD: Allergy to stinging insects. Ann Allergy 1993;70:427

27. Tunget CL, Clark RF: Invasion of the "killer" bees. Postgrad Med 1993;94:92

28. Ariue BK: Multiple Africanized bee stings in a child. Pediatrics 1994;94:115

29. Diaz-Sanchez CL, Lifshitz-Guinzberg A, Ignacio-Ibarra G, et al: Survival after massive (<2000) Africanized honeybee stings. Arch Intern Med 1998;158:925

30. Kolecki P: Delayed toxic reaction following massive bee envenomation. Ann Emerg Med 1999;33:114

31. Stafford CT: Hypersensitivity to fire ant venom. Ann Allergy Asthma Immunol 1996;77:88

Bruce Herman,Elisabeth Skokan. Bites that poison: A tale of spiders, snakes, and scorpions. Contemporary Pediatrics 1999;8:41.