The editors and current author would like to thank and acknowledge the significant contribution of the previous authors of this chapter from the 2004 first edition, Dr. Todd T. Kuwaye, and the 2015 second edition, Dr. Coral W. Yap. This current third edition chapter is a revision and update of the original authors’ work.

Case 1:
A 6-year-old female was found by her mother to be playing in the yard when she suddenly felt pain in her left ankle. Her ankle became swollen, red, and painful. Her mother took her to the pediatrician's office. Upon careful examination there is a central puncture lesion with a small amount of serosanguinous drainage. No other examination findings are relevant. Her vitals are normal.

Questions to consider when evaluating this patient:
What are the potential causes for this lesion?
What immediate treatment is needed?
What advice should be given to the child and parents?

On ECG there are narrow QRS complexes with sinus tachycardia on the monitor.

Many incidents of envenomations, bites and stings occur each year in the United States involving snakes, spiders, scorpions, other arthropods, and marine life. In Hawai'i, there are no venomous snakes. However, bites and stings from arthropods, spiders, scorpions, and marine life do occur. Patients most commonly present to the emergency department or outpatient setting for evaluation and treatment of confirmed or suspected envenomation. A clinician's careful assessment of the patient’s history to include signs and symptoms are important in guiding the diagnosis and therapy.

Bites

Animal and human bites are fairly common. The clinical manifestations of infections can often be very serious. Bites occur in 4.7 million Americans yearly and account for approximately 1% of all emergency department visits. The microbiology and infectious disease aspects of human, cat, and dog bites are bacteria associated with the environment, the victim's skin flora, and/or most important, the oral flora of the biter. In cats and dogs, the most common bacteria leading to infection after a bite are Pasteurella species with upwards of 50% in dogs (Pasteurella canis) and 75% in cats (Pasteurella multocida). In contrast, human bites most commonly lead to Staphylococcus, Streptococcus, Eikenella, and anaerobes including Fusobacterium species, Prevotella, and Peptostreptococcus infections (1). Routine wound care consists of wound irrigation to dilute bacterial counts and to cleanse the wound of foreign material, followed by debriding necrotic tissue, and removing any foreign bodies (1). Cat bite wounds tend to be smaller and deeper, rendering these more infection prone than the larger and more open wounds from dog bites that can be more easily irrigated and cleansed (1). Commonly, these do not undergo primary closure because of the increased infection risk. First line treatment is with an extended-spectrum penicillin with a beta-lactamase inhibitor (e.g., amoxicillin/clavulanic acid), while penicillin allergic patients can be treated with clindamycin plus trimethoprim-sulfamethoxazole. Ampicillin-sulbactam and carbapenems are recommended when parenteral antibiotics are needed (1). However, staphylococci can still be resistant to these combinations. Human bites generally have higher complication and infection rates than do animal bites, with human bites causing infection 10% to 15% of the time (1). Infection risk is based on the extent of tissue damage; depth of the wound and which compartments are entered. Bites to the hands tend to be fairly deep and frequently become infected. A fist to the teeth can result in a penetrating wound into the extensor tendon sheaths that appears small but is highly complication prone. Other considerations include immobilization of the affected area, including splinting if necessary, and elevation of the affected limb. Tetanus prophylaxis should be managed with human tetanus immune globulin along with tetanus toxoid-containing vaccine depending upon the vaccination status of the patient and wound. (1). Regarding rabies postexposure prophylaxis, immunocompetent and unvaccinated children should receive a 4-dose rabies vaccine series with human rabies immune globulin (1).

Snakes

There are thousands of species of snakes worldwide with approximately 15% being venomous. Venomous snakes, usually vipers (rattlesnakes, copperheads, cottonmouths, or water moccasins), bite approximately 5000 to 10,000 people in the United States annually. Of those bitten, the mortality rate is exceptionally low at 0.05%, usually encompassing children or elderly who have delayed or no antivenom therapy (2,3). The highest numbers of deaths are reported in North Carolina, Texas, and Arkansas. Globally, there is estimated to be between 1.2 million and 5.5 million persons bitten by snakes each year, with 20,000 to 94,000 resulting in death (3). Not all bites by venomous species cause clinical effects. Many of the snakes found in the U.S are non-venomous or only mildly toxic species and these snakes are responsible for the majority of bites. Envenomation can cause extensive tissue destruction and devitalization that predisposes to infection from the snake's normal oral flora.

The largest family of venomous snakes is Viperidae, which includes the subfamily of Crotalinae (formerly called Crotalidae), otherwise known as pit vipers (e.g., rattlesnakes, copperheads, and cottonmouths). Pit vipers are responsible for over 97% of envenomations annually in the United States. Many of the Pit vipers bites are "dry" when venom is not released (2).

The other venomous snake family is Elapidae, (e.g., cobras, coral snakes, and many species of Australian snakes). In this family the only snake indigenous to the United States is the coral snake. The coral snake has vivid bands of red, yellow, and black. A popular rhyme to identify the deadly coral snake found in the U.S. is, "Red on yellow, kills a fellow. Red on black, venom it lacks." This means that if red and yellow bands are adjacent to each other, this is a venomous coral snake. But if red and black bands are adjacent to each other, this is a non-venomous snake.

Snakebites are often witnessed and it is most important to identify which type of snake caused the envenomation. Individuals may have different responses to specific venoms. Often bites that appear to have caused minimal local effects may actually lead to very serious systemic consequences. For example, the venom from the pit viper (family Viperidae) and some elapids usually causes localized edema and pain that spreads proximally and after a few hours leads, to vesicular lesions and bullae, which are often hemorrhagic. The systemic sequelae of viper and some elapid bites include nausea, weakness, muscle fasciculations, changes in taste (metallic), sensory changes, renal dysfunction, shock, and systemic hemorrhage (3). Envenomation by certain neurotoxin releasing snakes, such as coral snakes (family Elapidae) classically presents first with ptosis and then progressive neuromuscular weakness including slurred speech, fasciculations, drowsiness, weakness, and respiratory failure. The venom blocks neuromuscular transmission at acetylcholine receptor sites. When death occurs in these cases, it is usually due to progressive paralysis of respiratory muscles (3).

Treatment of snakebites includes local wound care, which involves washing the site, irrigation, providing analgesia, and resting the extremity. The affected extremity should be closely examined for edema and signs of compartment syndrome while also assessing airway, breathing, and circulation (ABC's) in case systemic symptoms were to develop. Generally any patient who shows moderate to severe signs and symptoms after a venomous snakebite is a candidate for treatment. Initial treatment involves establishment of two IV lines in unaffected extremities, followed by fluid resuscitation with isotonic saline if there is evidence of hemodynamic instability. Vasopressors may be added after appropriate volume resuscitation and antivenom administration (3). Poison control centers can provide information about antivenom availability and other management recommendations. In Hawai'i anti-venom is not needed because there are no venomous snakes in the environment. Basic labs should be drawn to assess for hemorrhage or hemolysis, thrombocytopenia, liver function, and rhabdomyolysis. Additionally, in regards to rhabdomyolysis, urine should be tested for blood or myoglobin since patients are at an increased risk of developing acute kidney injury (3). Typing and cross-matching should be obtained in case a blood transfusion is needed.

Arthropods

Arthropods have at least a partly segmented body and a stiff external skeleton. This is the largest group of organisms with more species than all other groups combined in both Hawai'i and the world. The class Arachnida includes spiders, mites, scorpions, and its relatives who are all present in Hawai'i. Class Chilopoda includes centipedes with the rock centipede (family Lithobiidae) being native to Hawai'i. The scolopendra is the largest centipede reaching up to 12cm in length and is capable of inflicting a painful bite.

There are over 40,000 species of spiders that have been identified with many more yet to be classified. Most bites cause minor and local skin irritation, which can lead to infection if not treated appropriately. In the United States, the black widow (Latrodectus species) and brown recluse (Loxosceles species) constitute the majority of medically significant envenomations. The black widow species is found throughout the U.S. and is identified by their shiny black bodies and red markings, which resembles a red hourglass on their ventral aspect. The brown recluse spider (Loxosceles reclusa) inhabits the South and Midwest. They may be colloquially referred to as "fiddleback" or "violin" spiders due to the dark fiddle or violin shaped marking on their dorsal aspect. Only rarely biting humans unless they feel threatened, these spiders usually cause only minor injuries with localized erythema and edema (4).

Unlike snakebites, spider bites often are difficult to identify since puncture marks are uncommon and often the patient may not have felt a bite. It is important to recognize the toxidrome (signs and symptoms associated with a medically significant spider bite) and obtain a detailed history especially when suspicious of spider envenomation. The black widow is a non-aggressive spider, which bites in self-defense. While black widow bites can cause severe muscle pain and neurological symptoms, they are rarely fatal (5). Its neurotoxic venom initially causes local, radiating pain proximally leading to regional lymph node tenderness within the first 30 to 120 minutes. Its appearance might be target-like (concentric circles) but it is more often circular and red with a raised central area. Severe muscle cramping and spasms may occur because of neurotoxin activity at the presynaptic membrane causing the release and decreased uptake of acetylcholine, norepinephrine, and other neurotransmitters. Dysautonomia manifested with nausea, emesis, sweating, hypertension, tachycardia, and malaise can also occur. Typically, the pain begins to resolve in the first 12 hours, but may persist for days or weeks before resolving (4). Treatment is generally supportive to include analgesia for significant pain and treatment of hypertension and tachycardia if dysautonomia were to develop. Antivenom derived from horse serum is available but reserved only for the most severe cases due to the adverse effects and risk of anaphylaxis. Of note, pediatric patients being treated with high doses of opioids or benzodiazepines for symptomatic relief, are at risk for developing central nervous system and respiratory depression. Dantrolene treatment is often mentioned but it does not shorten the duration of symptoms, and is not recommended (5).

Other types of spiders known to have necrotic venom are those found in the Sicariidae family, which includes both the brown recluse and six-eyed sand spiders. These bites can cause a central blister and develop into a necrotic center. Systemic reactions are infrequent and usually can be treated with supportive care. These symptoms can include fever, chills, arthralgias, nausea, and emesis. Very rarely, severe complications such as shock, renal failure, disseminated intravascular coagulation, and even death may occur.

Scorpions are related to spiders. They have four pairs of legs and a long curling tail with a stinger at the end. Scorpions primarily inhabit the Southwestern U.S. Most species are not dangerous to humans; however, the bark scorpion (C. exilicauda formerly sculpturatus) found in Arizona and New Mexico harbors a poisonous venom. Scorpions are found in Hawai'i but their venom is not significantly toxic. These envenomations tend to result in a simple painful and very localized reaction that can be treated supportively with analgesics and antihistamines, as well as antivenom therapy (6). The more severe cases can result in neurologic compromise with respiratory and cardiovascular collapse.

In general, scorpions are not aggressive and tend to hide in crevices, under footboards, and burrow outside during the day to avoid the light. They are nocturnal creatures. Humans typically are stung on their hands and feet after accidentally encroaching on the scorpions’ hiding places.

Stings from the Arizona bark scorpion may require antivenom therapy if there are signs of systemic neurotoxicity. The antivenom, which was first approved by the FDA in 2011, is effective in reducing symptoms within 4 hours as well as reducing levels of circulating venom (7). The antivenom is only available in Arizona.

Arthropod stings more commonly occur from bees, wasps, and ants amongst others. All of these arthropods contain mild venoms. Systemic allergic reactions occur more frequently from insect stings compared to insect bites in children. Stinging insects belonging to the order Hymenoptera (bees, wasp, and ants) are responsible for 40 to 50 deaths per year in the United States (8). Reactions to arthropod stings can be classified as usual, large local, anaphylactic, and toxic reactions. The usual arthropod sting causes local pain, swelling, and erythema, which resolve in a few hours. Large local reactions involve more extensive symptoms of extreme erythema and increased swelling to the site of the sting that continues to spread over 24 to 48 hours (9). Anaphylaxis is potentially life threatening and requires emergent treatment. Anaphylaxis is more common with envenomations by bees and wasps. Signs and symptoms include skin reactions in other parts of the body other than the site of envenomation, difficulty breathing, swelling of the tongue or throat, nausea, vomiting, and/or signs of shock (lightheadedness, weak and thready pulse, hypotension). A toxic reaction occurs from envenomation from multiple stings due to an accumulation of the venom in the body. This can cause headache, vertigo, fainting, convulsion, fever, vomiting, and diarrhea.

The initial management is to remove the stinger. The stinger of the bee is barbed and detaches after being imbedded into the victim's skin. Since wasps can sting repeatedly, one may find grouped lesions without any visible stinger. The bee stinger contains venom sacs which if pinched can increase the level of envenomation. It is recommended to scrape the stinger out of the skin using a blade, credit card, a fingernail, or forceps followed by an ice pack applied to the affected areas to slow down venomous spread (8). Usually, local reactions of insect stings require control of pain, pruritus, and swelling, as well as local wound care to prevent infections. Localized hypersensitivity reactions can be treated with topical corticosteroids and urticaria can be treated with antihistamines. Anaphylactic reactions are treated aggressively with intramuscular epinephrine and other anaphylaxis measures (8).

Repeat anaphylactic reactions to insect stings are more common in adults than in children. Children and adults with generalized skin reactions after stings have a 10% incidence of subsequent systemic reactions and a less than 1% incidence of a life-threatening allergic reactions (9). Children's sensitivity to insect venom is expected to diminish over time. An allergist should evaluate any child with an anaphylactic reaction to insect stings. Immunotherapy for insects can be used on children depending on the severity of the allergic reaction. Any child with a history of anaphylaxis and a positive skin test or in vitro assay for venom specific IgE could benefit from immunotherapy for 4 to 5 years (9). In children with large localized reactions who are at risk for future frequent or multiple stings, immunotherapy is an option. These children should also be given a self-administered epinephrine kit with instructions and a demonstration of its use (9). Patients should also obtain a medical alert bracelet.

Marine Envenomations

Marine envenomation is very common in Hawai’i. They can occur from jellyfish, Portuguese man-of-war, and venomous fish. Jellyfish and Portuguese man-of-war envenomate using stinging cells called nematocysts that produce a protein-based venom. Stingrays have venomous spines on their long tails. As a general rule, these venoms tend to be optimized in cold water and are thus heat labile and can be denatured with heat. These types of stings cause severe pain to the skin and can leave whip like erythematous welts that can last 24 to 72 hours after the initial insult. Most often the pain subsides quickly especially if application of hot water (just above 40 degrees C, 104 degrees F) is used to the affected area for 15 to 30 minutes which is thought to the denature the protein-based venom. Commonly used treatments with vinegar and meat tenderizer (papain) are less effective than heat. The affected area should be soaked immediately in non-scalding hot water until significant pain relief, or approximately 30 to 90 minutes (3). More severe allergic reactions can cause fever, shock, and cardiopulmonary compromise, although this is extremely rare.

There are about 1,200 types of venomous fish, including lionfish, catfish, scorpionfish, weever fish, toadfish, surgeonfish, rabbitfish, stargazers, and stonefish. They have spines on their dorsum that release the venom. In the case of the stonefish and possibly other types of venomous fish, they may be stepped on and release venom into the victim's feet. They cause localized reactions similar to jellyfish and Portuguese man-of-war and can be treated using the application of hot water.

Questions
1. A ten-year-old male is stung by a bee. Upon examination of the sting site, a stinger is still embedded in the skin. What should you do?
   a. Pinch it off
   b. Scrape it off
   c. Wait till you seek medical attention

2. A twelve-year-old male moving boxes in the basement experienced a pinprick sensation on his right hand followed by muscle cramps and swelling in his right axilla. On presentation to the ER a target lesion is noted on his right hand. The patient is noted to be nauseated, sweating, hypertensive, and tachycardic. What is the probably culprit?
   a. Centipede
   b. Scorpion
   c. Yellow jacket
   d. Black widow
   e. Brown violin spider

3. True/False: Ticks, flies and mosquitoes can cause anaphylaxis.

4. True/False: Repeat anaphylactic reactions to insect stings are more common in adults than in children.

5. What two spiders in the U.S. can inflict a serious and potentially deadly envenomation?

6. A teenage boy fishing is accidentally poked by a spiny fish. The site becomes red and painful. Which is NOT a reasonable step in the approach to management?
   a. Local wound care
   b. Epinephrine
   c. Application of heat to sting site
   d. Antibiotic ointment
   e. Tdap immunization
   f. Contact a poison information center

References
1. Bula-Rudas FJ, Olcott JL. Human and Animal Bites. Pediatr Rev 2018;39(10):490-500. doi.org/10.1542/pir.2017-0212
2. Greene SC, Folt J, Wyatt K, Brandehoff NP. Epidemiology of fatal snakebites in the United States 1989-2018. Am J Emerg Med 2021;45:309-316. doi.org/10.1016/j.ajem.2020.08.083
3. Lei C, Badowski NJ, Auerbach PS, Norris RL. Chapter 451. Disorders Caused by Venomous Snakebites and Marine Animal Exposures. In: Jameson JL, Fauci AS, Kasper DL, Hauser SL, et al (eds). Harrison’s Principles of Internal Medicine, 20th edition. 2018. McGraw-Hill Education, New York, NY. pp:2733-2744.
4. Hubbard JJ, James LP. Complications and Outcomes of Brown Recluse Spider Bites in Children. Clin Pediatr 2011;50(3): 252-258. doi: 10.1177/0009922810388510
5. Glatstein M, Carbell G, Scolnik D, Rimon A, Hoyte C. Treatment of pediatric black widow spider envenomation: A national poison center’s experience. Am J Emerg Med 2018;36(7):998-1002. doi.org/10.1016/j.ajem.2017.11.011
6. Bahloul M, Chabchoub I, Chaari A, et a. Scorpion Envenomation Among Children: Clinical Manifestations and Outcome. Am J Trop Med Hyg 2010;83(9):1084-1092. doi: 10.4269/ajtmh.2010.10-0036
7. Boyer LV, Theodorou AA, Berg RA, et al. Antivenom for Critically Ill Children with Neurotoxicity from Scorpion Stings. New Engl J Mede 2009;360:2090-2098. doi: 10.1056/NEJMoa0808455
8. Zirngibl G, Burrows HL. Hymenoptera Stings. Pediatr Rev 2012;33(11): 534-535. doi.org/10.1542/pir.33-11-534
9. Pansare M, Seth D, Kamat A, Kamat D. Summer Buzz: All You Need to Know about Insect Sting Allergies. Pediatr Rev 2020;41(2):348-356. doi.org/10.1542/pir.2018-0358

Answers to questions
1.b
2.d
3.True, anaphylaxis can occur from any repeated insect bite or sting in which re-exposure to an antigen occurs, but this is relatively uncommon for these particular arthropods.
4.True
5.Southern black widow and brown recluse spider.
6.b