Envenomations

EXECUTIVE SUMMARY

• Most wounds attributed by the patient to spider bites are, in reality, local skin infections.

• Large local reactions from hornets, wasps, yellow jackets, and bees can mimic cellulitis.

• Scorpion stings cause intensive local pain followed by paresthesias that typically spread over several hours.

• About one in four pit viper bites does not produce symptoms or signs of envenomation. These are termed “dry bites.”

• Clinical manifestations of envenomation from both pit vipers and coral snakes can be delayed up to 12 hours, so a period of observation is necessary.

Envenomations can occur from a variety of species, both marine and non-marine. They can cause symptoms that range from minor skin irritation to systemic signs and symptoms, organ failure, and even death. Knowing which venomous species are endemic to the area can help with identifying envenomations, especially when the bite or sting is unwitnessed or the patient is unable to identify the species. Be cautious when bites or stings are suspected but unwitnessed by the patient; local infections or necrotic wounds often are attributed incorrectly by the patient to a “spider bite.” Knowing the signs and symptoms of envenomation are important for management and disposition. Treatments often include wound management, pain control, and supportive care. Sometimes antivenom is an option. Poison control centers and medical toxicologists can help with treatment and disposition for envenomations.

This article will give an overview of the medically important envenomations, with a focus on nonmarine envenomations in the United States. It will discuss clinical manifestations, diagnosis, treatment, and disposition.

Arachnids

Arachnida is a class of arthropods that includes spiders. Spiders inject venom into their prey. Most spiders do not have clinically significant bites for humans. Of the thousands of spider species, most are not powerful enough to penetrate human skin, and most have little or no effect on human tissues.¹ Additionally, most spiders only bite in extreme circumstances. Medically important spiders in the United States include brown recluse and black widow spiders.

Systemic allergic reactions to spiders are rare. However, local reactions can occur from contact with a spider. Most cases are from contact with large spiders with urticating hairs, such as tarantulas.^2,3

Local reactions to spider bites can include papules, pustules, and wheals. There can be redness and a tender nodule at the bite site. Some wounds turn necrotic. Discomfort can range from a burning or itching sensation to severe pain, or there may be no discomfort at all and the bite may go unnoticed.⁴

Systemic reactions to spider contact or bites can include proximally spreading pain, hypertension, tachycardia, diaphoresis, paresthesias, and vomiting. See Table 1 for a summary of envenomations and treatments for each spider.

Brown Recluse Spiders

Loxosceles spiders, also known as recluse spiders or fiddleback spiders, are known for their bites that sometimes become necrotic. Brown recluse spiders (L. reclusa) are the most common and widespread species of recluse spiders in the United States. It is estimated that 10% of bites from Loxosceles spiders will become necrotic,⁵ but this estimate may be falsely elevated because other necrotic lesions are incorrectly attributed to Loxosceles spider bites.

Loxosceles spiders often are identified by the violin or fiddle appearance on their back. However, the violin marking may be absent in juvenile spiders and in some species of Loxosceles.⁶ Additionally, some nonvenomous spiders have markings that can be misinterpreted as a violin shape so that the spider is misidentified as a recluse spider. Other brown spiders also are mistaken for brown recluse spiders.⁷ The best way to identify Loxosceles spiders is to count the number of eyes. Most spiders have eight eyes, but the Loxosceles species have six eyes.⁶ Unfortunately, most spiders are not captured for identification following a bite, making identification difficult based on description alone.

Brown recluse spiders live in the central Midwest and mid-southern states. Other Loxosceles species live along the southern parts of Texas to California. They usually are found in dark, quiet, dry areas of homes, such as attics, basements, and closets. They also are found outdoors in places like wood piles.⁸

Clinical Manifestations. The venom of brown recluse spiders contains cytotoxic enzymes, including hyaluronidase and sphingomyelinase-D.⁹ Bites of brown recluse spiders generally are painless initially. Usually, mild erythema will develop in the first eight hours, and then it fades over days to weeks. Sometimes wounds will turn necrotic. These wounds start with pain and erythema within hours at the bite site and progress to a hemorrhagic blister surrounded by blanched skin and outer erythema. By day 3-4, the hemorrhagic blister will become ecchymotic, causing a “red, white, and blue” lesion (outer erythema, inner blanching, and central ecchymosis). The central area may become necrotic and develop an eschar by days 5-7. The wound will ulcerate and heal slowly. Some wounds even may require skin grafting.^8,9 The term often used to describe necrotic wounds from spider bites is dermonecrotic arachnidism.

Systemic symptoms are rare with brown recluse spider bites. Hemolysis can occur one to three days (and even up to seven days) after a bite. Hemolysis is more common in children. Fevers, chills, vomiting, and arthralgias are some systemic symptoms that can occur. Thrombocytopenia, rhabdomyolysis, and renal failure can occur. Disseminated intravascular coagulation (DIC) and death are rare.^8,9

Diagnosis. The diagnosis of a recluse spider bite depends on the history and physical exam findings. No laboratory tests are readily available for detecting spider venom. A definitive diagnosis can be made only if the spider was observed biting the patient, was collected and subsequently identified, and the history and physical exam findings correlate with the spider in question.¹⁰ A presumptive diagnosis of a spider bite can be made based on the history and physical exam and a location in an endemic area, but one should consider the differential diagnosis first. Often, infections, dermatitis, or other conditions are misdiagnosed as spider bites.⁶

In a study of 182 patients who presented to the emergency department with a “spider bite,” researchers found that only seven patients (3.8%) had an actual diagnosis of spider bite. Eighty-five percent of patients were diagnosed with an infection rather than a spider bite.¹¹

Patients are not the only ones who incorrectly identify a spider bite as the cause of their symptoms. Physicians also misdiagnose spider bites. In a study from Florida, researchers compared brown recluse spider bites reported by physicians to the Florida poison centers in a six-year period to verified findings of Loxosceles spiders in Florida over a 100-year period. They found that 124 bites were reported by medical personnel during a six-year timespan, but only 11 confirmed finds (consisting of about 70 individual spiders) occurred during a 100-year timespan in Florida.¹² The authors concluded that Florida did not have sufficient populations of Loxosceles spiders to account for the reported frequency of dermonecrotic arachnidism.

In another article, researchers reviewed 134 case studies from 91 journal articles and found that only 22% of cases had verified spider bites.¹³ This means that even physicians can falsely attribute skin infections to spider bites.

The differential diagnosis of spider bites includes community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections that can appear similar to spider bites. CA-MRSA skin and soft tissue infections typically present as furuncles, carbuncles, and abscesses, but they also can present as a single pustule similar to a spider bite. They also can progress to necrotic lesions, similar to some spider bites.¹⁴

Herpes simplex and herpes zoster can produce single or multiple vesicular lesions, which can be confused with brown recluse bites. Tzanck staining and viral culture can be used to confirm herpes infections.

Lyme disease also is on the differential. The rash of early Lyme disease can start as a papule or macule and then expands to become a circular area of erythema or a target lesion, known as erythema migrans. Erythema migrans can progress to ulceration and necrosis.¹⁵ This often leads to the misdiagnosis of a necrotic spider bite. The geographic location can help with diagnosis, since the natural environment of ticks carrying Lyme disease is different than the natural environment of Loxosceles spiders that cause necrotic skin lesions. Lyme testing, such as ELISA and Western blot, can be performed as needed.

Insect bites and stings, such as those from biting flies, mosquitoes, and ticks, also can be confused with spider bites. Insect bites and stings are far more common than spider bites. Allergic reactions and tick-borne illnesses are the clinically important consequences of insect bites and stings. Otherwise, knowing which specific insect is the culprit is not as important.⁴

Dermatitis from poison ivy and poison oak can be misdiagnosed as a spider bite, especially when it presents as a single lesion rather than the classic linear lesions.⁴ Pyoderma gangrenosum is an inflammatory disorder that can cause painful ulcers, and may have a similar appearance to a necrotic spider bite. It is diagnosed by skin biopsy. Cutaneous vasculitis can cause ulceration and necrosis, and may sometimes present as a single lesion, which can be confused with pyoderma gangrenosum or with a spider bite. As with pyoderma gangrenosum, skin biopsy can aid in diagnosis.⁶

A mnemonic that has been proposed to help differentiate brown recluse spider bites from other diagnoses is NOT RECLUSE. It stands for Numerous (brown recluse bites are usually singular); Occurrence (did the bite happen in a typical recluse habitat); Timing (bites do not usually happen in winter months); Red center (bites usually have a pale center); Elevated (bites are flat); Chronic (lesions do not usually last several weeks); Large (lesions are not usually > 10 cm); Ulcerates too early (bites usually ulcerate after seven days); Swollen (significant swelling is atypical); Exudative (not usually exudative).¹⁶

When a brown recluse spider bite is suspected, and the patient is having systemic signs or symptoms, blood work, including complete blood count (CBC), basic metabolic panel (BMP), creatine kinase (CK), and coagulation studies, should be obtained. Other studies can be obtained as indicated to rule out alternate diagnoses.

Treatment. Management typically is supportive. This involves pain management and local wound care, including washing the wound, elevation, and use of ice packs. The cytotoxic enzyme sphingomyelinase-D is temperature-dependent, making ice packs a good strategy to prevent the progression of necrosis.¹⁷ Antibiotics are indicated when there is a secondary wound infection, but this is uncommon. Update tetanus immunization. Surgical debridement typically is delayed by two to three weeks after the bite, once clear margins are established. This is because ongoing tissue injury can occur prior to the two- to three-week mark.⁸

Currently, Loxosceles antivenom is unavailable in the United States, but it is available in some areas of South America. South American Loxosceles species can cause more severe bites and a higher risk of necrotic wounds and systemic signs and symptoms. In South America, antivenom is recommended for anyone with systemic signs and symptoms after a bite and for those with moderate to severe necrosis within 48 hours of a bite.⁶

Systemic symptoms, such as hemolytic anemia, thrombocytopenia, and rhabdomyolysis, are treated with standard therapies. Studies of additional therapies specific to brown recluse envenomation have not found consistent benefit.

Steroids have been suggested in cases of hemolytic anemia, but few studies have evaluated steroid use in hemolytic anemia after brown recluse envenomation. In a case series of nine adult patients with suspected brown recluse envenomation and systemic symptoms, researchers found that there was no significant difference in the time to recovery from hemolysis, but the patients who received steroids required fewer blood transfusions overall.¹⁷

Few human studies have been done to evaluate steroid use for necrotic wounds of brown recluse spider bites. One approach incorporated prednisone, in addition to aspirin and antibiotic therapy, for 20 patients with brown recluse spider bites in Missouri. Patients had favorable outcomes for both systemic symptoms and necrotic wounds.¹⁸

Hyperbaric oxygen may be considered in brown recluse spider bite wounds of various sizes that fail to heal with local wound care, steroids, and antibiotics over two to three months.¹⁹ However, benefit is not consistent.

Therapeutic plasma exchange can be considered in refractory hemolytic anemia due to brown recluse envenomation, but large studies are lacking.²⁰

Dapsone has been suggested by some, but many recommend avoiding its use. No good human studies have been done to show benefit. Additionally, there is a risk of methemoglobinemia and hemolytic anemia, as well as hypersensitivity reactions with dapsone.^1,6

At this time, local wound care and delayed surgical debridement appear to be the best treatment options in the United States.

Disposition. Hospitalization is recommended for patients with systemic signs and symptoms. In patients with local reactions, discharge is acceptable, but the patient should have outpatient follow-up for serial wound exams. Children without systemic signs and symptoms can be discharged home, but with good follow-up and return instructions because of the risk of hemolysis days after the bite.^6,9

Black Widow Spiders

Black widow spiders (Latrodectus) are found worldwide. In the United States, medically significant envenomations are most commonly attributed to the western black widow spider (L. hesperus) and the southern black widow spider (L. mactans).

Latrodectus spiders typically are identified by the red hourglass marking on their body. However, not all species have a perfect hourglass appearance. Sometimes, the marking appears as two separate triangles or as one triangle with a small red mark below it. Many Latrodectus spiders are black, but some are brown or red. They typically are found outdoors in garages, sheds, and woodpiles, and occasionally in gardening gloves and tools.^8,21

False black widow spiders (Steatoda spp.) are from the same family as black widows and have a similar appearance. However, their bites are less serious than those of true black widow spiders.²¹

Clinical Manifestations. The main toxin that causes symptoms in black widow spider bites is α-Latrotoxin, which causes presynaptic release of catecholamines and acetylcholine. The bite is felt as a pinprick sensation. Erythema develops within one hour of the bite. Localized diaphoresis occurs near the bite site. A target lesion with a blanched center may develop.

Muscle cramping and spasms frequently occur, and this pain can progress from the affected extremity to the abdomen, back, and trunk. Abdominal muscle spasms can mimic an acute abdomen. Systemic symptoms include nausea, vomiting, diaphoresis, headache, photophobia, and shortness of breath. Local paresthesias and tremor may occur.

Hypertension and tachycardia commonly occur. Myocarditis, atrial fibrillation, pulmonary edema, and priapism are rare. Infants and young children may present with irritability, diffuse erythema, excessive salivation, muscle tremors and weakness, tetany, and seizure-like activity. Skin necrosis and secondary infection are rare in black widow spider bites.^8,21

A review of the National Poison Data System found that from the years 2000 to 2008, a total of 23,409 Latrodectus spider exposures were reported from 47 states. Of these, roughly 10,000 had symptoms and were reviewed further. The majority of patients had only minor symptoms. Only 1.4% of cases had life-threatening or disabling symptoms. No deaths were reported.²²

Diagnosis. There is no laboratory test that can confirm a black widow envenomation. Witnessing the offending spider and having characteristic signs and symptoms can be used for a clinical diagnosis. Consider an electrocardiogram (ECG) to evaluate for dysrhythmia. Consider a chest X-ray to assess for pulmonary edema when hypoxia, respiratory distress, or abnormal lung sounds are present. Obtain other testing as indicated, such as laboratory testing and imaging when the patient presents in a manner similar to an acute abdomen.

Treatment. For mild envenomations, or grade 1 envenomations, signs and symptoms are limited to local skin reactions and localized pain, with no significant spread of pain and no systemic signs or symptoms. Give oral pain medications as needed, including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, and sometimes opioids.²³ Oral muscle relaxers, such as benzodiazepines, have been suggested. However, there is no good evidence to show effectiveness, and adverse events are more common in those patients receiving benzodiazepines.²²

Grade 2, or moderate, envenomations involve spreading pain. Grade 3, or severe, envenomations involve spreading severe pain with systemic findings. Intravenous (IV) opioids and benzodiazepines are used for severe pain and muscle spasms.²³

Antivenom (Antivenin [Latrodectus mactans] manufactured by Merck) is a treatment consideration for moderate to severe envenomations. In North America, American black widow spider (L. mactans) antivenom is available, and a new experimental Latrodectus equine immune F(ab)2 antivenom (Analatro) just underwent a Phase III trial to evaluate efficacy and safety. It is not yet available for use.

Antivenom is recommended for moderate to severe envenomations that are unresponsive to supportive care measures.²³ The L. mactans antivenom has been in short supply, and the decision to use antivenom should be made in consultation with a medical toxicologist. For both adults and children, one vial can be given initially. If there is no clinical improvement, a second and third vial can be administered at hourly intervals.²³

Antivenom has been shown to significantly reduce the duration of symptoms and to reduce the severity enough that patients can be discharged safely home.^23,24,25 The L. mactans antivenom has resulted in allergic reactions and anaphylaxis. One death was reported in a patient receiving this antivenom, but this patient had multiple drug allergies and asthma, and received undiluted antivenom as an IV push.⁸

During a Phase III trial, the new experimental Latrodectus antivenom showed a significant difference in treatment failures between antivenom and placebo. In the placebo group, 24 of the 31 patients (77.4%) failed to achieve and maintain adequate pain control, compared to 15 of the 29 patients (51.7%) in the antivenom group (P = 0.019). Additionally, no serious adverse events were reported related to the antivenom, nor were allergic reactions or deaths.²⁶

IV calcium gluconate previously was recommended for the treatment of black widow envenomations. However, further studies found it to be ineffective in treating symptoms.²⁴ Methocarbamol, a muscle relaxant, also has been studied and has been shown to be fairly ineffective in treating symptoms.²⁷ Another muscle relaxant, dantrolene, has been evaluated with no proven efficacy.²⁸

Patients who continue to have uncontrolled hypertension despite adequate pain control may be treated with standard antihypertensives. However, beta-blockers generally should be avoided, especially when antivenom administration is considered. This is because of the risk of counteracting the therapeutic effect of epinephrine should it be needed in treating anaphylaxis from antivenom.^9,29

Disposition. Patients with mild envenomations can be discharged home. Many patients with moderate to severe envenomations can be discharged home after receiving antivenom. The exact length of ED observation following antivenom administration is not established. However, one study involved an average of two hours of observation following antivenom administration.³⁰

Hospitalization is required for those with ongoing or worsening signs and symptoms, and those who require IV pain medications.^9,23 Those who receive antivenom and develop allergic symptoms should be hospitalized for ongoing observation. Consider admission for patients who remain hypertensive despite antivenom and pain control.³¹

Other Spiders

Tarantulas are large, hairy spiders that often are kept as pets, but they also can be found naturally in the southwestern United States. The hairs found on the abdomen can be used defensively and can penetrate human skin, although North American species are less likely to penetrate human skin. Hairs that penetrate the skin can cause pruritus. Hairs also can penetrate the conjunctiva and cornea of the eye, and should be suspected when a patient presents with eye redness and pain after handling a tarantula. Tarantula bites are painful and can cause local redness and swelling. Fever can occur, but other systemic signs and symptoms are very rare. Hairs can be removed by applying and then removing duct tape. For ocular toxicity, topical steroids can be considered in consultation with an ophthalmologist. Cleaning the wound and providing supportive care with analgesics and antihistamines are recommended.^8,9

Phoneutria, or armed spiders (armadeiras), usually are found in South America. There have been reports of these spiders hiding in banana bunches during shipping and biting workers at destination sites. Bites can produce severe pain. Hypertension, tachycardia, nausea and vomiting, diaphoresis, and priapism can occur. Death from respiratory failure can occur quickly, within two to six hours, especially in children. In most cases, supportive care is sufficient. Antivenom exists, but it is unavailable in the United States. Opioids for pain control should be used with caution, since they can augment the venom effects on respiration. Consider regional pain management with local anesthetic infiltration at the bite site.^4,8

Yellow sac spiders are found in North America and are very aggressive. Bites are painful, with redness and swelling. Nausea and headache may occur. Treatment includes symptomatic treatment and wound care.^4,8

Hobo spiders have been found in the Pacific Northwest of the United States and Canada. Necrotic wounds similar to brown recluse bites have been attributed to hobo spider bites, but have not been proven.³²

Hymenoptera

Hymenoptera stings cause more fatalities than any other arthropod. This class includes the Vespidae (hornets, wasps, and yellow jackets), Apidae (honeybees and bumblebees), and Formicidae (ants, including imported fire ants).⁸

Vespidae and Apidae

Clinical Manifestations. The venom of Vespidae and Apidae has many components, including phospholipase A (a strong allergen), hyaluronidase (breaks down tissue to allow venom penetration), and histamine (contributes to pain and itching). Bee venom also contains melittin (cytotoxic) and apamin (neurotoxic). Hornet and wasp venom contains acetylcholine (increases stimulation of pain nerves).³³ These and other venom components are responsible for the symptoms of local reactions and anaphylaxis, and for the toxic effects of massive envenomations.

The most common reaction to Vespidae and Apidae stings is a local reaction consisting of erythema, swelling, pain, and pruritus. These develop within minutes of a sting and usually resolve over a few hours. Some people develop large local reactions, with a larger area (about 10 cm in diameter) of erythema and swelling. The erythema and swelling spread over the first 48 hours and gradually resolve over the next five to 10 days.³⁴

Secondary bacterial infection is uncommon. Large local reactions often are confused with secondary bacterial infections. Infection should be suspected when erythema, swelling, and pain are increasing three to five days after a sting. Large local reactions start improving after the first two days. Fever also suggests infection. However, lymphangitis streaks can be seen with both infection and large local reactions.³⁴

Anaphylaxis is a concerning reaction to a sting. Symptoms can range from mild to rapidly fatal. Death can happen within minutes.⁸ Flushing, urticaria, and angioedema are common skin symptoms. Shortness of breath due to upper airway edema and wheezing due to bronchoconstriction can occur. Nausea, vomiting, diarrhea, and abdominal cramping can be seen. Hypotension and cardiovascular collapse can occur with severe anaphylaxis.

The risk of anaphylaxis from future stings is a concern for many patients. In adults with a history of anaphylaxis to stings and who have venom-specific immunoglobulin E (IgE), the risk of recurrent anaphylaxis with a subsequent sting is 30-70%.³⁵ Children with a history of moderate to severe anaphylaxis to a sting have a 32% chance of recurrent anaphylaxis to a sting in the future.³⁶

Local reactions, large local reactions, and anaphylaxis can occur after one or a few stings. Massive envenomation can occur after many stings. This can cause vomiting and diarrhea, lightheadedness and syncope, involuntary muscle spasms, convulsions, and fever. Rhabdomyolysis, renal failure, liver failure, and disseminated intravascular coagulation (DIC) can occur.⁸ Honeybees and bumblebees can sting only once because their sting apparatus detaches from their body after a sting. However, hornets, wasps, and yellow jackets are able to withdraw their stinger and sting multiple times. Renal failure has been seen after as few as 20-30 wasp stings.³⁷

Massive envenomations also can be seen from Africanized honeybees. Africanized honeybees, or killer bees, are found in the southern United States. They are more aggressive and can swarm and attack with more than 10 times the number of bees than with a typical North American bee. More than 50 stings in an adult and more than one sting per kilogram in a child have a risk of massive envenomation. Death can occur after hundreds of stings.⁹

A delayed reaction of serum sickness-like illness can occur five to 14 days after a sting. Signs and symptoms include polyarthritis, lymphadenopathy, urticaria, fever, and malaise.⁸ Other uncommon reactions include myocarditis, vasculitis, neuritis, and encephalitis. These can occur days to weeks after a sting.³⁴

Diagnosis. The history and physical examination are sufficient for diagnosis. Further diagnostics, especially with massive envenomations, include renal and hepatic function, ECG and troponin, CK, and DIC panel.

Treatment. Bee stingers that are lodged in the skin should be flicked off immediately, or as soon after a sting as possible. Venom generally is released from the stinger within seconds of a sting,³⁴ and stingers should be removed as soon as possible to prevent any remaining venom from being injected. Scraping off the stinger using the edge of a credit card is a safe, quick method to dislodge a stinger.

Cold compresses can be used for local reactions. Large local reactions can be treated with cold compresses, NSAIDs for pain, antihistamines and topical corticosteroids for itching, and oral prednisone.³⁴ When secondary bacterial infection is suspected, treatment with an oral antibiotic is indicated. Anaphylaxis from a sting is treated the same as other causes of anaphylaxis, including epinephrine, corticosteroids, and H1 and H2 antihistamines. (See Table 2.)

Venom immunotherapy can reduce the risk of a recurrence of anaphylaxis to a sting to about 5% in both children and adults.^36,38 Refer patients who develop anaphylaxis after a Hymenoptera sting to an allergist for consideration of immunotherapy.³⁹

Give supportive care and standard treatments for other complications, such as IV fluids for rhabdomyolysis. Bee antivenom for massive envenomations is not yet available but is being studied.⁴⁰

Disposition. Admission for observation should be considered for patients with massive envenomation (> 50 stings in adults and > one sting/kg in children). Admission criteria for anaphylaxis after a sting are the same as for other causes of anaphylaxis. Patients with other significant complications, such as myocarditis and encephalitis, also should be admitted. Patients with uncomplicated stings can be discharged home. Prescribe an epinephrine autoinjector to those with anaphylactic reactions to a sting, and refer to an allergist for follow-up.

Formicidae

Imported fire ants are aggressive and will swarm and sting with little provocation. They hold on to the skin with their strong mandibles and can sting repeatedly if not removed promptly. Red imported fire ants can be found in the southern United States. Black imported fire ants are found in parts of Alabama, Mississippi, and Tennessee.⁴¹

Clinical Manifestations. Fire ant venom contains phospholipase A, hyaluronidase, and histamine, similar to bees, wasps, and hornets. The venom also contains piperidine alkaloids, which contribute to the pain of fire ant stings.³³

The first symptoms to present after a sting from an imported fire ant are erythema, painful burning, and pruritus. Within 24 hours, a sterile pustule will develop for each sting. Secondary bacterial infection can occur when the pustules are opened. Sometimes they are opened when the patient scratches the area, and sometimes they are opened because the patient thinks they are infected already and need to be drained.³⁴ A large local reaction has a large area of erythema and edema. An extreme local reaction can cause swelling severe enough to cause vascular compromise.⁴¹ Anaphylaxis is reported in 0.6-16% of patients.⁴¹ Rhabdomyolysis, acute renal failure, and cardiopulmonary symptoms resulting in death can occur with massive attacks, yet other people recover without complications.^8,41

Diagnosis. Diagnosis is made by the history and physical examination. Consider obtaining an ECG and laboratory studies, including BMP and CK, with massive attacks.

Treatment. Antihistamines and topical corticosteroids can provide itch relief. Oral antibiotics are indicated if a secondary bacterial infection develops. A high-potency topical steroid or oral prednisone can help with large local reactions. Anaphylaxis is treated with standard therapies. (See Table 2.)

Caterpillars

Caterpillars have protective hairs and spines, and the spines are attached to a venom gland. Pruritus, a rash known as “caterpillar dermatitis,” and sometimes urticaria can occur from contact with caterpillar hairs and venom (this is called erucism). Adhesive tape can be used to remove caterpillar hairs and spines from the skin. Cool compresses, antihistamines, and steroids can be given for itching.

Caterpillar hairs also can affect the eye, similar to tarantula hairs. Conjunctivitis, keratitis, conjunctival and iris nodules, and chorioretinopathy can develop. Ophthalmia nodosa is the term given to ocular conditions resulting from contact with caterpillar hairs. Treatments include irrigation of the eye, topical antibiotics and steroids, sometimes systemic steroids, and removal of nodules and caterpillar hairs by an ophthalmologist.⁴²

The puss caterpillar (Megalopyge opercularis) can cause a severe burning sensation, grid-like hemorrhagic papular rash, lymphadenopathy, and edema. Fever, hypotension, and convulsions also can occur. Supportive care with systemic analgesics and benzodiazepines for pain and muscle spasms can be given. IV fluids and epinephrine should be given for hypotension.⁸

Blister Beetles

Blister beetles contain cantharidin toxin, also called Spanish fly. Cantharidin-containing products can be used for wart removal and have been used as an aphrodisiac. Contact with this toxin in high concentrations can produce blisters and bullae. If contact with the eye occurs, the toxin can cause severe conjunctivitis known as Nairobi eye. Ingestion of blister beetles or cantharidin-containing products can cause vomiting, diarrhea, gastrointestinal bleeding, and abdominal pain, followed by hematuria and dysuria, oliguria, and renal failure.⁸

Blister beetles should be removed from the body by blowing or flicking, since the toxin is released from the joints of the beetle when it is disturbed or crushed. Irrigation of the skin can remove residual toxin. Ophthalmologists can help with ocular exposures. Ingestions are treated with supportive measures. Admission is warranted for patients who are symptomatic after ingestion.⁸

Scorpions

Scorpions are invertebrate arthropods that can be found worldwide, including the southern parts of the United States. Local pain after a sting is common, but the bark scorpion (Centruroides exilicauda) found in Arizona, New Mexico, and parts of California and Texas, has venom that can cause systemic signs and symptoms, and even death, especially in children.

Clinical Manifestations. A scorpion sting will cause sudden, intensive local pain followed by a tingling sensation or paresthesias. Bark scorpions do not cause local tissue destruction. Neuromuscular toxicity can develop and can be life-threatening. Envenomation is categorized by severity. Grade I envenomation involves local pain and/or paresthesias. Tapping the sting site as the patient is looking away will increase the pain significantly. This is known as the “tap test” and is characteristic of bark scorpion stings. Grade II envenomation includes local as well as proximally spreading or remote pain and/or paresthesias. Grade III envenomation causes either cranial nerve dysfunction or skeletal neuromuscular dysfunction, with or without autonomic dysfunction.

Cranial nerve dysfunction includes slurred speech, dysphagia, abnormal eye movements (usually slow, conjugate, wandering movements, but sometimes opsoclonus with rapid multidirectional movements) and blurred vision, and tongue fasciculations. Increased oral secretions and bulbar neuromuscular dysfunction can cause airway problems.

Skeletal neuromuscular dysfunction includes fasciculations, shaking and jerking of the extremities, restlessness, and alternating arching (opisthotonos) and flexion of the back. Autonomic dysfunction includes vomiting, salivation, diaphoresis, bronchoconstriction, and tachycardia.

Grade IV envenomation involves both cranial nerve and skeletal neuromuscular dysfunction and can have autonomic dysfunction. Hyperthermia, metabolic acidosis, pulmonary edema, rhabdomyolysis, and multi-organ failure also have occurred rarely.⁴³

Diagnosis. Characteristic signs and symptoms of envenomation, along with travel to or living in an endemic area and a history of a scorpion sting, confirm the diagnosis. For grade III and IV envenomations, laboratory testing including renal and hepatic function and CK are indicated.

The differential diagnosis, especially when the scorpion sting was unwitnessed, includes black widow spider bite, tetanus, strychnine poisoning, botulism, neuroblastoma, organophosphate toxicity, seizure, and meningitis. Black widows can cause similar autonomic dysfunction, but without the abnormal eye movements and fasciculations. Tetanus and strychnine poisoning can cause painful muscle contractions, including opisthotonos, similar to scorpion envenomation, and tetanus can involve autonomic dysfunction. However, these lack the abnormal eye movements seen with scorpion envenomation.

Botulism can cause cranial nerve dysfunction along with symmetric weakness. Unlike scorpion envenomation, botulism tends to lack fever and has symmetric neurologic symptoms, with no sensory deficits or pain. Neuroblastoma can involve abnormal eye movements and jerking of the extremities, but without pain, excessive salivation, skeletal neuromuscular dysfunction, or acute onset of symptoms. Organophosphate toxicity can cause excessive salivation and fasciculations, but it also can cause paralysis and seizures, which are not seen with scorpion envenomation.

Scorpion envenomation can have alternating arching and flexion of the back similar to a seizure, but seizing patients generally do not have normal mental status. Fever and stiffness of the neck can be seen with both scorpion envenomation and meningitis, but meningitis lacks the abnormal eye movements seen in scorpion envenomations.⁴³

Treatment. Grade I and II envenomations can be treated with pain control, including NSAIDs, opioids, and regional anesthesia. Clean the wound and administer tetanus prophylaxis. For grade III and IV envenomations, supportive care and airway management are important. Antivenom is recommended. Young children and pregnant women also should receive antivenom.

A study evaluating critically ill children after a scorpion sting found that scorpion-specific F(ab’)(2) antivenom (Alacramyn in Mexico and Anascorp in the United States) showed more rapid resolution of symptoms, resolution of symptoms in all antivenom recipients by four hours, and undetectable plasma venom concentration at one hour after treatment.⁴⁴

Benzodiazepines can be used for muscle spasms in patients who are not receiving antivenom. Caution should be used when giving benzodiazepines and antivenom together, since over-sedation can occur.⁴³ Using short-acting benzodiazepines, such as midazolam, can decrease this risk. Atropine can be considered for hypersalivation from Centruroides stings. However, some scorpions outside of the United States cause an autonomic storm, and atropine use in these cases can worsen toxicity.⁸

Disposition. Patients with grade I and II envenomations should be observed for four hours to ensure no progression of symptoms.⁴³ They can then be discharged home if no progression is seen. For grade III and IV envenomations, after patients receive antivenom and on sign and symptom resolution and vital sign normalization, patients can be discharged home. Patients with grade III and IV envenomations with persistent signs and symptoms, persistent abnormal vital signs, the need for IV analgesia, and intubation require admission.⁹

Snakes

Crotalinae and elapidae envenomations are discussed in the following section. Table 3 summarizes snake envenomations and their specific treatments.

Crotalinae

Members of the subfamily Crotalinae include rattlesnakes, copperheads, and water moccasins (cottonmouths). They are collectively called pit vipers. Pit vipers have heat-sensing pits behind the nostrils that help to locate and attack prey. They also have two hinged fangs that fold against the top of the mouth, unlike to the elapids that have fixed fangs. Pit vipers have triangular shaped heads, slit-like pupils, and a single row of subcaudal plates. As the name implies, rattlesnakes also have rattles.

Rattlesnakes live throughout the United States, except for Maine, Alaska, and Hawaii, and are concentrated in the southwestern United States. Copperheads are found along the eastern coast from Connecticut to Georgia, and extending west to Texas. Water moccasins live along the southern United States from Virginia to Texas.

Clinical Manifestations. Pain and swelling at the bite site and ecchymosis can develop within minutes, and hemorrhagic blebs can occur within hours.

Bites to the face or neck can cause edema with resulting airway obstruction. Bites to an extremity can cause severe edema and, in rare cases, can develop into compartment syndrome. More commonly, the severe edema from envenomation is mistaken for compartment syndrome when compartment syndrome is not actually present. Increased vascular permeability and extravasation of fluid into the subcutaneous tissues can cause hypovolemia with hypotension, tachycardia, and tachypnea.

Systemic toxic effects include coagulopathy and thrombocytopenia, rhabdomyolysis, and neurotoxicity with oral paresthesias, fasciculations, and altered mental status.^9,45 Anaphylaxis can occur in 1-2% of pit viper bites.⁴⁶ Other systemic symptoms include nausea, vomiting, diarrhea, chills, and generalized weakness.

Envenomation severity is categorized as minimal, moderate, and severe. Bites that occur without the patient developing signs or symptoms of envenomation are called dry bites. One in four pit viper bites is a dry bite.⁴⁷ It should be noted that sometimes signs and symptoms of envenomation are delayed by several hours, so a dry bite can be diagnosed only after a period of observation.

Minimal envenomations involve only local tissue effects. Moderate envenomations include a large area of tissue effects, but less than a full extremity, along with non-life-threatening systemic signs and abnormal coagulation studies without bleeding. Severe envenomations involve tissue damage to an entire extremity and tissue damage with resulting airway compromise or signs of compartment syndrome, life-threatening systemic signs, and abnormal coagulation with severe bleeding.⁴⁶

Rattlesnake envenomation is more severe compared to water moccasin envenomation. Copperhead envenomations usually involve local tissue effects without systemic signs and symptoms.⁴⁶

Diagnosis. A history that fits with exposure to a snake, the presence of fang marks, and signs and symptoms of envenomation are needed to make the diagnosis of snake bite with envenomation. If the first two criteria are met but without signs or symptoms of envenomation for eight to 12 hours, then a diagnosis of a dry bite can be made.

Laboratory studies should include CBC, BMP, CK, and coagulation studies, including fibrinogen and D-dimer.

Treatment. Treatment should start with addressing airway, breathing, and circulation. Intubation may be required in patients with bites near the face or neck. Hypovolemia and hypotension need to be addressed early with IV fluids and vasopressors if needed. Other supportive measures include pain management (avoiding NSAIDs because of coagulopathy and thrombocytopenia) and treating electrolyte derangements.

The patient should remain calm and still, and the injured area should be kept still and elevated in both the prehospital and ED settings. Tourniquets to cut off arterial inflow are contraindicated since they produce damaging ischemia. Venous compression bandages have no proven benefit and should be avoided. Mark and time the leading edge of tenderness and swelling every 15-30 minutes. Wound management includes cleaning the wound and updating tetanus immunization. Wound infections are rare. In a study of 2,748 rattlesnake bites, only about 1% developed infection.⁴⁸

Crotalidae polyvalent immune Fab (ovine) (Fab AV or CroFab) is an antivenom for crotalinae envenomations. A medical toxicologist consultation is recommended before giving antivenom. Phone consultation can be achieved by calling a regional poison control center. See Table 4 for the CroFab treatment algorithm.⁴⁹ Pregnancy is not a contraindication to antivenom administration.

A study of patients with crotalinae bites who received CroFab found that initial control was achieved in 82.2% of patients. Neurotoxicity and thrombocytopenia were associated with difficulty in achieving initial control.⁵⁰

Another study found that initial control was achieved in 87% of mild to moderate envenomations and 57% of severe envenomations. Immediate hypersensitivity reactions (anaphylactic and anaphylactoid) to antivenom occurred in 6% of patients, and delayed hypersensitivity reactions (serum sickness) developed in 5% of patients.⁵¹ Anaphylaxis can be managed using standard treatments. Serum sickness, characterized by fever, rash, and arthralgias, can be treated with prednisone.

There is a risk of recurrent and late coagulopathy up to seven days after CroFab administration, as well as a risk of persistent coagulopathy despite antivenom therapy. Patients with rattlesnake or water moccasin bites should have coagulation studies rechecked at two to three days and five to seven days after the bite.⁴⁶

Crotalidae immune F(ab’)2 (equine) (Anavip) is another antivenom that is approved for rattlesnake envenomations. Anavip has similar efficacy to CroFab and similar rates of adverse reactions, but with less risk of delayed coagulopathy. Ten vials of Anavip (for both adult and pediatric patients) can be given in moderate to severe rattlesnake envenomations, with repeat dosing of 10 vials every hour until local signs of envenomation have stopped progressing, systemic symptoms are resolved, and coagulation parameters have normalized or are trending toward normal. Although there is less risk of delayed coagulopathy with Anavip, it is still recommended that patients have coagulation studies rechecked two to three days and five to seven days after the bite.⁴⁶

Fasciotomy of the affected limb based on physical examination findings alone is contraindicated, as the local tissue damage from venom can mimic signs and symptoms of compartment syndrome. A Stryker device can be used to measure individual compartment pressures. After the site has been cleaned and the device zeroed, insert the needle into the desired compartment at an angle that is perpendicular to the skin. The insertion point depends on which compartment is being tested. If the delta pressure (the difference between the diastolic blood pressure and the compartment pressure) is 30 mmHg or less, this is suggestive of compartment syndrome. If true compartment syndrome is suggested, the limb should be elevated, and mannitol and antivenom at the severe envenomation dosing should be administered. If the delta pressure remains
30 mmHg or less after an hour, consider fasciotomy.⁴⁵

In coagulopathy and thrombocytopenia, crotalinae venom will inactivate transfusions of clotting factors and platelets. Therefore, antivenom should be administered first, and platelet/fresh frozen plasma transfusions should be reserved for severe bleeding despite antivenom.⁴⁶

Disposition. Consider hospitalization for observation and treatment of crotalinae bites. (See Table 4.) Follow-up to recheck coagulation studies should be arranged when it is indicated. If there was coagulopathy during the hospital stay or if the patient was bitten by a rattlesnake, instruct the patient to avoid contact sports, dental work, and surgery for two weeks. Instruct patients to watch for signs and symptoms of serum sickness.⁴⁶

Elapidae

Elapids include coral snakes, mambas, cobras, and sea snakes. Coral snakes of the United States include the Eastern coral snakes, Arizona (Sonoran) coral snakes, and Texas coral snakes (Micrurus). Eastern coral snakes are found mostly in Florida and the southern portion of bordering states. Arizona and Texas coral snakes are found in Arizona and Texas, respectively. Mambas live in Africa, and cobras live in Africa and Southeast Asia. Mambas, cobras, and other exotic elapids can be found in the United States in zoos. They also are kept as exotic pets. Coral snake bites are more common in the United States and will be the focus of this section.

Coral snakes latch and “chew” their victims, expelling venom as they do this. Coral snakes in the United States have brightly colored rings on their skin, with red and yellow rings next to each other. Red and black rings next to each other usually indicate a nonvenomous snake (king snake), although this rule does not hold true outside the United States. The phrase “red on yellow, kill a fellow; red on black, venom lack” is an easy way to remember venomous coral snakes vs. nonvenomous snake species.

Clinical Manifestations. There is minimal or no pain at the bite site, mild or no swelling, and no significant tissue damage. Fang marks are not always identified. Many bites do not result in envenomation. When envenomation does occur, nausea, vomiting, and abdominal pain can be seen. Neurotoxic effects include bulbar paralysis leading to double vision, difficulty speaking, and difficulty swallowing; respiratory failure from descending muscle weakness; and generalized weakness. These effects can be delayed by up to 12 hours. Coagulopathy is not common.⁵²

Diagnosis. Coral snakes usually are identified when they bite a patient, as many bites occur from direct handling. Coral snakes often have to be forcibly removed since they latch on and chew their victims.⁵² When the bite is not observed, consider alternative diagnoses, such as botulism and myasthenia gravis.

When a snake bite is involved but there is severe local tissue damage or evidence of coagulopathy, both suggesting a non-elapid bite, consider laboratory testing as discussed in the crotalinae section.

Pulmonary function testing, such as maximal inspiratory pressure (MIP), can be used to assess respiratory muscle weakness. Serial exams and close observation are needed.

Treatment. Immobilize the affected limb in a position below the level of the heart and consider pressure immobilization to delay systemic absorption of venom.⁵² Clean the wound and update tetanus immunization.

Serial pulmonary function tests can guide the need for respiratory support. For example, if the MIP falls below -30 cm H₂O, respiratory muscle weakness is worsening and mechanical ventilation is indicated. Forced vital capacity (FVC) less than 50% of predicted capacity, and maximal expiratory pressure (MEP) less than 40 cm H₂O, also are indications for mechanical ventilation. End-tidal CO₂ can detect hypoventilation, and arterial blood gases can look for impending respiratory failure. Antivenom should be given at the first sign of bulbar weakness.⁵³

If neurotoxicity is developing and there will be a delay in antivenom administration, one can consider anticholinesterase administration, such as neostigmine, pretreated with atropine. However, data on efficacy are not consistent. Consultation with a toxicologist should occur prior to administering neostigmine.⁵²

North American coral snake antivenom (Antivenin [Micrurus fulvius]) is indicated for all symptomatic coral snake envenomations, except for Arizona coral snake bites, for which the antivenom does not have an effect and the envenomations are not severe. Three to five vials should be given for both adults and children.⁵² Adverse reactions to the antivenom, such as allergic reactions and serum sickness, are common (18%), but life-threatening reactions like angioedema and hypotension are not common.⁵⁴ Allergic reactions and serum sickness can be treated with standard treatments.

Disposition. Admit all patients with coral snake bites. Asymptomatic patients may develop delayed neurologic symptoms up to 12 hours later, and, therefore, should be observed for 12-24 hours.⁵³ Patients requiring antivenom still can have progression of neurologic symptoms and, therefore, also require admission.⁵⁵

Poisonous Lizards

Gila monsters and Mexican beaded lizards (Heloderma) are poisonous lizards that are found in the southwestern deserts of the United States and northern Mexico. They also are found in zoos and kept as pets. They have grooved teeth with venom that contains gilatoxin. They have a strong bite and can be difficult to remove. Deep wounds and fractures can be seen. Dislodged teeth need to be removed from wounds.

Local wound care and tetanus prophylaxis are needed. Control pain. Dry bites do occur. When envenomation occurs, systemic toxicity includes diaphoresis, vomiting, paresthesias, generalized weakness, and severe hypertension. No antivenom is available, so these patients should receive supportive management. Anaphylactic and anaphylactoid reactions also can occur. (See Table 2 for anaphylaxis standard treatments.) Manage the airway as appropriate when angioedema occurs.⁴⁵

Conclusion

Envenomations can range from minor to severe signs and symptoms and sometimes can be fatal. Practitioners should be aware of venom effects and basic emergency treatments. Contacting a medical toxicologist or regional poison control center can be helpful with treatment, disposition, and knowing what to watch for.

REFERENCES

A complete list of references is available online: https://bit.ly/2MQamBK.