1323CHAPTER 112 Bites and Stings unnoticed or feels like a pinprick 48 The site typically develops a “target lesion” consisting of a central reddened, indurated area surrounded by an area of blanching[.]
CHAPTER 112 Bites and Stings 1323 • Fig 112.7 Black widow spider bite site (Courtesy Sean Bush, MD.) • Fig 112.6 Black widow spider (Latrodectus hesperus) (Courtesy Sean Bush, MD.) spiders build low-lying webs and are usually found in dark or dry places outside of homes—garages, barns, outhouses, woodpiles, underneath outdoor furniture, and outdoors.48,54 The brown widow spider varies in color from cream to almost black with red and yellow markings and is almost exclusively found outdoors (including patio furniture).48 Bites by black widow spiders generally occur on upper and lower extremities, when people don gloves or boots that have been in outdoor storage.48,55 Bites by males or immature black widow spiders typically elicit more mild symptoms owing to their smaller size, weaker oral musculature, and decreased venom.48 Because they tend to live in recessed locations, brown widow spider bites are most likely when people stick their fingers and exert pressure into places such as curled edges of potted plants or a grab hole of a plastic trash bin.48 Recluse Spiders Brown recluse spiders are tan in color without spots or stripes and often have a brown violin shape on the front of the body.48 The eye pattern is most distinctive, as they have six eyes arranged in pairs in a U shape, unlike the typical eight eyes in several rows on most spiders.48 Similar to widow spiders, recluse spiders are also found in dry, dark places outdoors; however, they are commonly found indoors as well, hiding in furniture, clothes, sheets, and cupboards.53 Most recluse envenomations occur on the legs when the spider is trapped against a human, such as when putting on clothes or rolling over during sleep, and are usually unnoticed.48,53 Pathophysiology and Clinical Presentation Widow Spider Envenomation (Latrodectism) Widow spider envenomation is referred to as latrodectism, which is characterized by neurotoxicity without significant local injury.49 Widow spider venom contains five neurotoxins, which induce repeated or sustained painful muscle contraction through massive neurotransmitter release at the presynaptic membrane of the neuromuscular junction.48,49,53,55 Classically, the bite is either • Fig 112.8 Latrodectus facies (Courtesy Sean Bush, MD.) unnoticed or feels like a pinprick.48 The site typically develops a “target lesion” consisting of a central reddened, indurated area surrounded by an area of blanching and an outer halo of redness (Fig 112.7).55 Puncture wounds may not be seen owing to the spider’s small fang size.54 Pain usually begins at the bite site (most commonly an extremity) within hour and may radiate centrally to the back, chest, or abdomen.48 Radiating pain to the abdomen may be so severe as to mimic an acute abdomen, with tenderness and rigidity.48,56 Patients may exhibit “Latrodectus facies” (Fig 112.8), characterized by spasm of facial muscles, flushing, edematous eyelids, and lacrimation, which can be mistaken for an allergic reaction Autonomic disturbances such as tachycardia, hypertension, and diaphoresis are also common and typically last for days.49 Hypertension is attributed to venom acting on vasomotor centers in the brainstem and spinal medulla or activation of cholinergic sympathetic ganglia, resulting in norepinephrine release and peripheral vasoconstriction.55 Diaphoresis may occur around the bite site, profusely, or in unusual patterns, such as below bilateral knees.48,53,55 In addition to neurotoxicity, envenomations may result in systemic symptoms such as nausea, vomiting, headache, and anxiety Unusual presentations have been described after widow spider envenomation, including myocarditis, cardiomyopathy, compartment syndrome, and priapism.57–60 Fatality is rare.48 1324 S E C T I O N X I I Pediatric Critical Care: Environmental Injury and Trauma Recluse Spider Envenomation (Loxoscelism) Recluse spider envenomation is referred to as loxoscelism Most (,90%) bites are either asymptomatic or result in a small, erythematous, self-resolving papule with local edema.48 However, more severe cases can result in dermonecrosis (,10%) or systemic loxoscelism (,1%).48 The exact pathophysiology of dermonecrosis is not fully understood, but hyaluronidase is responsible for direct tissue digestion; sphingomyelinase D is attributed with capillary endothelial tissue destruction, inciting an inflammatory response that causes further tissue damage, local ischemia from microthrombi, and hemolysis.53 Dermonecrotic lesions typically cause pain, pruritus, and erythema, leading to induration within to hours, then progressing to ecchymosis and, ultimately, necrosis and eschar formation over several days (range is hours to weeks).48 Dermonecrotic lesions above the neck raise the risk of airway compromise from localized swelling, particularly in children.48 Full healing may take several weeks to months.48,53 Systemic loxoscelism is rare but occurs more commonly in children and can be fatal within 12 to 30 hours.48 Metalloproteinases in the venom are thought to cause local hemolysis, triggering systemic inflammation that results in massive hemolytic anemia.48 Renal injury may ensue due to hemoglobinuria, rhabdomyolysis, and/or direct venom toxicity, and may require dialysis.48 Patients may present with fever, malaise, nausea, vomiting, arthralgias, pruritus, and oliguria and exhibit jaundice, petechiae, or morbilliform rashes.48 Emergency and Critical Care Latrodectism Management Diagnostic tests are generally not helpful after a widow spider bite.48,53 Clinical signs and symptoms should guide further studies— such as creatine kinase, chest radiography, electrocardiography, or echocardiography—given the rare reports of rhabdomyolysis, myocarditis, and cardiomyopathy following widow spider envenomation.48,53 Treatment for symptomatic widow spider envenomation should begin with pain management in all cases and escalate to antivenin in severe cases if pain control is not achieved after several hours.49 Pain management includes the use of nonsteroidal analgesics, escalation to opioid analgesics as needed, and the addition of small doses of benzodiazepines for muscle spasms.49,53 In retrospective studies, widow spider antivenin is associated with complete resolution of symptoms within ,30 minutes without recurrence, allowing for outpatient management.49,55 However, randomized clinical trials failed to prove effectiveness over placebo.61,62 For severe cases in the United States, one vial of the available antivenin, Black Widow Spider Antivenin (Merck), should be reconstituted in 2.5 mL of the sterile diluent supplied, then further diluted into 50 mL of normal saline and administered intravenously over 15 minutes.49 Widow spider antivenin is derived from horse serum and thus has a risk of life-threatening hypersensitivity reaction.55,63,64 Though the risk of hypersensitivity is relatively low,53 antivenin should be reserved for those with serious systemic symptoms.49 Ultimately, the risk of hypersensitivity to antivenin must be weighed against the potential benefit of relieving prolonged discomfort Admission to the hospital and possibly the pediatric ICU is prudent for severely symptomatic children, those with intractable pain and contraindications to antivenin, and those who have anaphylaxis to antivenin Patients who experience relief with opioid analgesics, benzodiazepines, or antivenin may be discharged.49 Antibiotics are not indicated unless there is evidence of cellulitis Tetanus prophylaxis should be updated as appropriate.49 Loxoscelism Management Mild cases of recluse spider envenomations are generally selflimiting In the setting of dermonecrosis or systemic loxoscelism, diagnostic studies should include creatine kinase, urinalysis and assessment of renal function, complete blood count, coagulation studies, type and screen, as well as markers of hemolysis (i.e., lactate dehydrogenase, haptoglobin, bilirubin, reticulocyte count) An assay for detecting Loxosceles venom from wound samples to better diagnose recluse spider envenomations is under investigation.48,65 Dermonecrosis can be treated with supportive measures—such as cold compresses, rest, and watchful waiting—rather than surgical debridement.48 To optimize healing and minimize disfiguration, debridement should be done only for very severe necrotic wounds once the necrosis has stopped spreading.48 Children with systemic loxoscelism should be admitted to the hospital and may require ICU care for severe hemolysis and/or renal failure.52 Globally, treatment for systemic loxoscelism has included a wide range of therapies, each with limited evidence and some with potential for harm: antivenin, corticosteroids, dapsone, antihistamines, antibiotics, analgesics, hyperbaric oxygen, electric shock, and surgical excision.53 Recluse spider antivenin is not available in the United States, but it is used in Central and South America.53 Corticosteroids and supportive care with transfusions and dialysis have been used with overall positive outcomes.48 Dapsone was used for many years but is no longer recommended owing to potential for significant toxicity and worse outcomes.48 Therapeutic Complications Potentially fatal anaphylaxis has been documented following treatment with black widow spider antivenin.55,63,64 Such reports warrant risk assessment for predisposition to anaphylaxis, proper antivenin dilution, and preparation of medications to treat anaphylaxis prior to slow administration of antivenin.48 Risk factors for anaphylaxis include allergy or prior exposure to horse serum, or a history of asthma Both of the referenced cases of death following antivenin treatment were in individuals with a history of asthma Skin testing is not recommended because it has not been shown to predict hypersensitivity, though patients should be considered high risk if the testing is performed and positive.49 Patients with asthma, allergies to horse serum products, or positive skin tests may benefit from pretreatment with antihistamine or corticosteroids as well as slower infusion of antivenin.49 Serum sickness days to weeks after treatment with antivenin may occur in up to 10% of cases and is typically managed on an outpatient basis with antihistamines and steroids.53 Follow-up On discharge, patients who received antivenin for widow spider envenomation should be educated regarding the signs of serum sickness and advised to follow up if these symptoms develop Following hospitalization for significant dermonecrosis or systemic loxoscelism after recluse spider bite, wound checks and/or follow-up studies of renal function may be indicated Patients should be counselled that spider bites may be prevented by eliminating the spider’s food and habitat; shaking sheets, shoes, and clothing before donning; keeping the child’s bed away from the wall; and brushing spiders off rather than crushing them CHAPTER 112 Bites and Stings Prognosis Widow spider envenomation syndrome usually resolves completely, with or without treatment The majority of recluse spider envenomations, even those causing dermonecrosis or systemic loxoscelism, also resolve completely with adequate supportive care.52 Pitfalls Misdiagnosing an acute abdomen in a patient with a widow spider envenomation could lead to unnecessary surgery On the other hand, misdiagnosing various skin lesions such as cellulitis, pyoderma gangrenosum, neoplasm, or Lyme disease as a recluse spider bite could result in delays in appropriate care and worse outcomes.48 Future Directions Safer antivenins are being developed and investigated, including a black widow spider antivenin consisting of highly purified equine F(ab)2 fragments.61 Resources The AAPCC may be helpful with management of spider envenomations and can be contacted at 800-222-1222 Scorpion Stings Epidemiology Scorpion stings are a serious medical problem worldwide.66,67 In the United States, over 105,000 scorpion exposure cases were reported to poison control centers from 2010 to 2015.68 Scorpions are found in the arid southwestern states, including California, with particularly high incidence of exposures in Arizona, Texas, and Nevada.66,68 However, all physicians should be prepared to manage scorpion stings, as there have been reported cases of stings during domestic or international airplane travel to states outside of the Southwest.66 Dangerous scorpions in the United States are in the family Buthidae The species most commonly implicated in serious envenomations is Centruroides sculpturatus.66 Many children and infants died from C sculpturatus stings in the early to mid-1900s, likely due to loss of airway protection, metabolic acidosis, hyperthermia, and rhabdomyolysis.66 However, mortality has drastically declined with improvements in supportive care, including airway management; a single death has been reported in the literature since 1970, which was attributed to anaphylaxis rather than toxic venom effects.66 Clinical Presentation Scorpions are not innately aggressive but will sting in self-defense, holding prey in their claws (pedipalps) and hooking their segmented tail over their own body to inject venom using the terminal stinger (telson).66,69 Most scorpion stings cause intense localized pain without significant tissue injury.67 About 10% of cases result in systemic neurotoxic envenomation (most commonly in children), characterized by neuromuscular abnormalities, respiratory failure, and cardiogenic shock.69 Direct neurotoxicity to somatic 1325 and cranial nerves can lead to uncoordinated movements, such as wild limb thrashing, muscle spasms, oculomotor abnormalities, and respiratory paralysis.69 Neuroexcitation of the parasympathetic system typically causes early cholinergic symptoms, including bronchospasm and increased secretions that can contribute to respiratory failure.69 Stimulation of the sympathetic nervous system and massive endogenous catecholamine release may lead to arrhythmias, myocardial injury, cardiogenic shock, pulmonary edema, and multiorgan failure.69 Acute pancreatitis has also been reported after stings by some scorpion species Emergency and Critical Care Immediate medical care following a sting is essential and can improve prognosis.67 Diagnostic studies should focus on the potential complications, including assessment of renal function and screening for pancreatitis.69 An electrocardiogram should be obtained in the setting of arrhythmia or in children with severe envenomation and concern for myocardial injury Additional cardiac studies, such as enzymes and echocardiogram, should be considered based on clinical presentation.69 Treatment includes supportive care and antivenin administration.67 Mild cases with localized pain can be managed with analgesia alone.67,69 Severe envenomations may require inotropic support, specific vasodilators (prazosin, nitroglycerin), mechanical ventilatory support, and/or benzodiazepines for sedation and neuromuscular pain.69 Clinical trial evidence for the use of antivenin is mixed, though a small North American trial of Centruroides envenomation demonstrated improved resolution of neurotoxic effects in those treated with antivenin compared with placebo.70 If given, antivenin should be administered promptly because it binds toxins to prevent further insult but does not reverse clinical manifestations, such as pulmonary edema or shock.67,69 Hymenoptera Stings (Bees, Wasps, and Ants) The order Hymenoptera comprises multiple medically important insect groups, including bees (Apoidea); wasps, hornets, and yellow jackets (Vespoidea); and ants (Formicidae), which all deliver venom through stings.71 Bee and vespid venoms are quite similar and contain histamine, dopamine, norepinephrine, and bradykinin-like substances as well as multiple enzymes involved in mastcell degranulation and tissue injury.71,72 Most stings result in an immediate local, self-limiting reaction consisting of erythema, edema, and pain in nonallergic victims.71,72 The majority of deaths are due to anaphylaxis (immunoglobulin E–mediated type I hypersensitivity) from a single sting in susceptible individuals.71,73 More rarely, massive envenomations can be fatal even in nonallergic individuals owing to delayed toxic— rather than immune-mediated—effects of the large quantity of venom itself.71–73 Massive bee and wasp envenomations are the focus of this section Massive Envenomation Africanized honeybees, characterized by their highly defensive behavior, have been most commonly associated with massive envenomation in the United States.74 However, all bees and vespids may be provoked, and massive yellow jacket envenomation in a child has been reported.72 Massive envenomation can initially produce immediate toxicity, resulting in fatigue, nausea, and vomiting, as well as hemolysis, 1326 S E C T I O N X I I Pediatric Critical Care: Environmental Injury and Trauma kidney failure, and disseminated intravascular coagulation.75 Some patients may initially be asymptomatic and have normal laboratory results but hours to days later develop severe complications, including rhabdomyolysis, multisystem organ failure, and death.72,74–77 Thus, a high index of suspicion and close monitoring are essential.72 In most mammals, the estimated lethal dose is 20 stings/kg,71 which places small children at potentially higher risk of severe effects.72 No pediatric deaths have been reported due to delayed toxic effects following massive Hymenoptera envenomation in the United States though, unfortunately, there have been several cases worldwide.72,74 Emergency and Critical Care Owing to the concern for delayed effects warranting intervention, all children with 50 or more stings should be admitted for at least 24 hours.75 Diagnostic studies should include laboratory evaluation for hemolysis, liver and renal injury, rhabdomyolysis, and disseminated intravascular coagulation.72 Studies should be obtained on presentation, hours later, and as indicated by the clinical picture.72 Treatment is generally supportive and may include IV fluids, pain control, dialysis, and transfusion as needed.72,75 Plasmapheresis has also been beneficial in renal failure, suggesting that it might remove circulating toxin or inflammatory mediators.72 Prognosis Most victims of massive envenomation are expected to recover with timely and adequate supportive care in a hospital setting as well as sufficient observation for delayed onset of severe symptoms.73 Key References Fitzgerald KT, Flood AA Hymenoptera stings Clin Tech Small Anim Pract 2006;21(4):194-204 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(6):998-1002 Gold BS, Barish RA, Dart RC North American snake envenomation: diagnosis, treatment, and management Emerg Med Clin North Am 2004;22(2):423-443, ix Gutierrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA Snakebite envenoming Nat Rev Dis Primers 2017; 3:17079 Isbister GK, Bawaskar HS Scorpion envenomation N Engl J Med 2014;371(5):457-463 Isbister GK, Fan HW Spider bite Lancet 2011;378(9808):2039-2047 Lavonas EJ, Ruha AM, Banner W, et al Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop BMC Emerg Med 2011;11:2 Skolnik AB, Ewald MB Pediatric scorpion envenomation in the United States: morbidity, mortality, and therapeutic innovations Pediatr Emerg Care 2013;29(1):98-103; quiz 104-105 Vetter RS, Visscher PK, Camazine S Mass envenomations by honey bees and wasps West J Med 1999;170(4):223-227 Vetter RS Spider envenomation in North America Crit Care Nurs Clin North Am 2013;25(2):205-223 The full reference list for this chapter is available at ExpertConsult.com e1 References Chippaux JP Snake-bites: appraisal of the global situation Bull World Health Organ 1998;76(5):515-524 Gutierrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA Snakebite envenoming Nat Rev Dis Primers 2017; 3:17079 Kasturiratne A, Wickremasinghe AR, de Silva N, et al The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths PLoS Med 2008;5(11):e218 Habib AG, Brown NI The snakebite problem and antivenom crisis from a health-economic perspective Toxicon 2018;150:115-123 Harrison RA, Hargreaves A, Wagstaff SC, Faragher B, Lalloo DG Snake envenoming: a disease of poverty PLoS Negl Trop Dis 2009;3(12):e569 Lang P, Chipman CW, Siden H, Williams RG, Norwood WI, Castaneda AR Early assessment of hemodynamic status after repair of tetralogy of Fallot: a comparison of 24 hour (intensive care unit) and year postoperative data in 98 patients Am J Cardiol 1982;50(4):795-799 Burki T Resolution on snakebite envenoming adopted at the WHA Lancet 2018;391(10137):2311 Longbottom J, Shearer FM, Devine M, et al Vulnerability to snakebite envenoming: a global mapping of hotspots Lancet 2018;392(10148): 673-684 Schulte J, Domanski K, Smith EA, Menendez A, Kleinschmidt KC, Roth BA Childhood Victims of Snakebites: 2000-2013 Pediatrics 2016;138(5) 10 Gold BS, Barish RA, Dart RC North American snake envenomation: diagnosis, treatment, and management Emerg Med Clin North Am 2004;22(2):423-443, ix 11 Warrell DA Snake bite Lancet 2010;375(9708):77-88 12 Hughes A Observation of snakebite victims: is twelve hours still necessary? Emerg Med (Fremantle) 2003;15(5-6):511-517 13 Goto CS, Feng SY Crotalidae polyvalent immune Fab for the treatment of pediatric crotaline envenomation Pediatr Emerg Care 2009;25(4):273-279; quiz 280-272 14 Hardy DL Fatal rattlesnake envenomation in Arizona: 1969-1984 J Toxicol Clin Toxicol 1986;24(1):1-10 15 McKinney PE Out-of-hospital and interhospital management of crotaline snakebite Ann Emerg Med 2001;37(2):168-174 16 Gold BS, Dart RC, Barish RA Bites of venomous snakes N Engl J Med 2002;347(5):347-356 17 Avau B, Borra V, Vandekerckhove P, De Buck E The Treatment of Snake Bites in a First Aid Setting: A Systematic Review PLoS Negl Trop Dis 2016;10(10):e0005079 18 Bush SP Snakebite suction devices don’t remove venom: they just suck Ann Emerg Med 2004;43(2):187-188 19 Bush SP, Hegewald KG, Green SM, Cardwell MD, Hayes WK Effects of a negative pressure venom extraction device (Extractor) on local tissue injury after artificial rattlesnake envenomation in a porcine model Wilderness Environ Med 2000;11(3):180-188 20 Watt G, Padre L, Tuazon ML, Theakston RD, Laughlin LW Tourniquet application after cobra bite: delay in the onset of neurotoxicity and the dangers of sudden release Am J Trop Med Hyg 1988;38(3):618-622 21 Bush SP, Hardy DL Sr Immediate removal of extractor is recommended Ann Emerg Med 2001;38(5):607-608 22 Bush SP, Cardwell MD Mojave rattlesnake (Crotalus scutulatus scutulatus) identification Wilderness Environ Med 1999;10(1):6-9 23 Bush SP, Green SM, Moynihan JA, Hayes WK, Cardwell MD Crotalidae polyvalent immune Fab (ovine) antivenom is efficacious for envenomations by Southern Pacific rattlesnakes (Crotalus helleri) Ann Emerg Med 2002;40(6):619-624 24 Sasaki J, Khalil PA, Chegondi M, Raszynski A, Meyer KG, Totapally BR Coral snake bites and envenomation in children: a case series Pediatr Emerg Care 2014;30(4):262-265 25 Dart RC, McNally J Efficacy, safety, and use of snake antivenoms in the United States Ann Emerg Med 2001;37(2):181-188 26 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(1):33-39 27 Dart RC, Seifert SA, Boyer LV, et al A randomized multicenter trial of Crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States Arch Intern Med 2001;161(16):2030-2036 28 Gerardo CJ, Quackenbush E, Lewis B, et al The efficacy of Crotalidae polyvalent immune fab (Ovine) antivenom versus placebo plus optional rescue therapy on recovery from copperhead snake envenomation: a randomized, double-blind, placebo-controlled, clinical trial Ann Emerg Med 2017;70(2):233-244 e233 29 Lavonas EJ, Gerardo CJ, O’Malley G, et al Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite Ann Emerg Med 2004;43(2): 200-206 30 Schaeffer TH, Khatri V, Reifler LM, Lavonas EJ Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis Acad Emerg Med 2012;19(2):121-131 31 U.S.F.D.A Expiration Date Extension for North American Coral Snake Antivenin (Micrurus fulvius) (Equine Origin) Lot L67530 through January 31, 2020 U.S Food & Drug Administration Available at: https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm630270.htm Published 2019 Updated February 1, 2019 Accessed April 10, 2019 32 Theakston RD, Warrell DA Crisis in snake antivenom supply for Africa Lancet 2000;356(9247):2104 33 CroFab [prescribing information] Nashville, TN 2000 34 Lavonas EJ, Ruha AM, Banner W, et al Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop BMC Emerg Med 2011;11:2 35 Norris RLJ, Bush SP, Auerbach PS North American Venomous Reptile Bites In: Wilderness Medicine 4th ed St Louis: Mosby; 2001 36 Gold BS, Barish RA, Dart RC, Silverman RP, Bochicchio GV Resolution of compartment syndrome after rattlesnake envenomation utilizing non-invasive measures J Emerg Med 2003;24(3):285-288 37 Hall EL Role of surgical intervention in the management of crotaline snake envenomation Ann Emerg Med 2001;37(2):175-180 38 Rosen PB, Leiva JI, Ross CP Delayed antivenom treatment for a patient after envenomation by Crotalus atrox Ann Emerg Med 2000;35(1):86-88 39 Tanen D, Ruha A, Graeme K, Curry S Epidemiology and hospital course of rattlesnake envenomations cared for at a tertiary referral center in Central Arizona Acad Emerg Med 2001;8(2):177-182 40 Toschlog EA, Bauer CR, Hall EL, Dart RC, Khatri V, Lavonas EJ Surgical considerations in the management of pit viper snake envenomation J Am Coll Surg 2013;217(4):726-735 41 Darracq MA, Cantrell FL, Klauk B, Thornton SL A chance to cut is not always a chance to cure- fasciotomy in the treatment of rattlesnake envenomation: A retrospective poison center study Toxicon 2015;101:23-26 42 Tanen DA, Danish DC, Clark RF Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model Ann Emerg Med 2003;41(3):384-390 43 Boyer LV, Seifert SA, Cain JS Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part Guidelines for clinical management with crotaline Fab antivenom Ann Emerg Med 2001;37(2):196-201 44 Seifert SA, Boyer LV Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part Pharmacokinetics and pharmacodynamics of immunoglobulin antivenoms and related antibodies Ann Emerg Med 2001;37(2):189-195 ... hemolysis.53 Dermonecrotic lesions typically cause pain, pruritus, and erythema, leading to induration within to hours, then progressing to ecchymosis and, ultimately, necrosis and eschar formation over... months.48,53 Systemic loxoscelism is rare but occurs more commonly in children and can be fatal within 12 to 30 hours.48 Metalloproteinases in the venom are thought to cause local hemolysis, triggering... retrospective studies, widow spider antivenin is associated with complete resolution of symptoms within ,30 minutes without recurrence, allowing for outpatient management.49,55 However, randomized