Loxosceles reclusa envenomation

Reviews

Loxosceles rechsa Envenomation BLAKE P. GENDRON, Loxocceles species are widely distributed. People are most al risk for bites when they disturb the nocturnal spider’s habitat. The bite sequelae range from insignificant, to disseminated intravascular coagulation and renal failure. Patients most frequently seek care for slow-healing necrotic skin lesions. Early surgical excision is not recommended. Conservative local care usually suffices. Dapsone may benefit some patients. Specific antivenom given early may minimize sequelae. (Am J Emerg Med 1990;8:51-54. 0 1990 by W.B. Saunders Company.) Spiders of the genus Loxosceles were first recognized by Macchiavello in Chile to cause gangrenous bites or necrotic arachnidism.‘v* The first clinical case of proven necrotic arachnidism in the United States was reported by a Kansas physician in 1929. However, it was not until 1957 that Atkins’ series confirmed that the powerful necrotoxin from Loxosceles could cause necrotic arachnidism.3-5 THE SPIDER There are 18 species in the genus Loxosceles found in and around North America, with 13 in the United States.6 Loxosceles reclusa (brown recluse) is the most common species in the United States and has been reported in at least 17 states. It is most prominent in the southern half of the Missouri-Ohio-Mississippi River basin and is also found in Tennessee, Kentucky, Georgia, Alabama, Indiana, Illinois, Iowa, Kansas, Oklahoma, Arkansas, Louisiana, Texas, and South Carolina.7,8 Spiders of the genus Loxosceles have a world-wide distribution. In South America, L rufescens has been found in Mexico, Brazil, and Paraguay; L laeta has been found in Argentina, Uruguay, Brazil, Chile, Peru, and Ecuador.’ There are at least 17 species of Loxosceles in Africa, and envenomations are well documented in South Africa.9V’o L rufescens has been documented throughout the Mediterranean countries, especially in Israel.” Other locations of Loxosceles infestation include China, Japan, Australia, and Southern Russia.‘*‘* From the Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA. Manuscript received November 14, 1988; revision accepted February 12, 1989. These are the personal opinions of the author, and are not to be construed as official views of Madigan Army Medical Center, the Army Medical Department, or the Department of the Army. Address reprint requests to LTC Gendron: Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA 98431-5302. Key Words: Loxosceles reclusa, skin ulcer, antirenin. 0 1990 by W.B. Saunders Company. 0735-6757/90/0801-0014$5.00/O

LTC, MC

The spider itself, L reclusa has six eyes arranged in three pairs. Adults range in size from 7 mm to 12 mm and average 9 mm. The legs and body of the spider are covered with very fine dark hairs and slightly larger cetae. The legs are very long and thin in relation to the body itself. Body color may vary from light fawn to dark brown, with darker-colored legs.6T’3 The spider has been nicknamed the fiddle-back spider from a violin-shaped stigma on the anterodorsal portion of the carapace. The namefiddle-back could also be applied to several other species, including L laeta, L rufescens, L unicolor, and L arizona.14 These spiders weave irregular, white, flocculent, adhesive webs that line their retreats.6 L reclusa is usually nocturnal and lives in warm, dry areas. such as undisturbed cellars or crawl spaces or abandoned buildings; woodpiles, fallen rocks, and similar sheltered areas are favored.r3 The largest populations may be found in indoor areas. L reclusa can live up to 6 months without food or water. It can tolerate temperature ranges from 8°C to 43°C but prefers temperatures from 23°C to 27”C.‘3,‘5 Female L reclusa have lived up to 1,400 days in simulated natural habitats, with an average life span between 1 and 3 years. The spider has been able to expand its habitat by traveling with people and their baggage; having shown up as far west as California and Hawaii and in unusual places such as Helsinki, Finland.‘5-‘8 The incidence of Loxosceles spider bites is difficult to detine. One study of 460 deaths from venomous bites in the United States between 1950 and 1959 reported 63 (14%) believed to be attributable to L reclusa.” A survey of 57 Texas counties for the period 1955 to 1960 disclosed 47 cases of suspected spider bites with necrotic skin lesions; only 5% of the polled physicians responded.20 A second survey of general practitioners in Kansas indicated that 80% had seen cases of loxoscelism; several had treated 30 or more such cases.*’ A large percentage of the estimated 3,333 spider bites treated by Mississippi physicians were presumed to be attributable to L reclusa.** Ticks, bed bugs, ants, biting flies, and other spiders can also inflict wounds that closely resemble mild cases of loxoscelism.23 PATHOPHYSIOLOGY The clinical spectrum of loxoscelism is divided into three major categories. The first, and possibly the most prevalent, includes bites in which little if any venom is injected. These bites may not be noticed by patients or reported to physicians.” A very mild reaction may also occur, characterized by formation of a small (S-mm) erythematous papule that can become very firm before healing. There may be 51

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localized urticarial response at the bite site for several days.24.25 In the second category, the spider bite is characterized by a cytotoxic reaction.s~8~26*27The bite may cause a mild stinging sensation or go completely unnoticed. Mild to severe pain usually appears 2 to 8 hours after the bite. Pain is followed by transient erythema and then blister formation at the site of the bite. Occasionally, there is a transient bluish discoloration within the first 24 hours, but usually the lesion turns from red to violet. The ischemia of the central blister or bleb causes necrosis in 3 to 4 days, with eschar formation between the fifth and the seventh days. The area becomes indurated and between 7 and 14 days the eschar falls off, leaving an ulceration that will heal by secondary intention.‘5 Lesions in fatty areas, such as the thighs, abdomen, and buttocks, tend to be more extensive and have more severe scar formation.2’ Ulcerations vary from 1 cm to more than 30 cm and may require 6 weeks to 4 months to hea1.28 The actual pathology of the lesion has been well studied in rabbit dermis.26,29 The necrosis (at least in the rabbit) is caused by activation of clotting mechanisms. Microthrombotic aggregates of leukocytes and platelets form a hemostatic plug in venules and arterioles, causing the necrosis. The third clinical category is systemic involvement occurring 24 to 48 hours after the bite. Children are particularly susceptible. 3o The syndrome includes fever, chills, weakness, edema, nausea, vomiting, joint pain, petechial eruptions, convulsions, and hemolysis.“s32 The hemolysis is apparently caused by a direct lytic effect of the spider venom on red cell membranes.33 The hemolysis can be severe, appearing in 2 to 3 hours and lasting up to 72 hours. This can lead to hemoglobinemia, hemoglobinuria, renal failure, and Diffuse intravascular coagulation may also be death. 26.34-35 present, probably triggered by hemolysis.34,36-38 The systemic symptoms are directly proportional to the amount of envenomation, but the severity of the skin lesions is not; outwardly minor skin lesions may be accompanied by hemolytic anemia.2”,33 There has also been one reported case of erythema nodosum after a brown recluse bite.3h The venom of L reclusa is complex. Various purification techniques have identified eight subcomponents. These include protease, alkaline phosphatase activity, lipase activity, sphingomyelinase D, and hyaluronidase activity.32.39-43 The sphingomyelinase D component may be the major factor related to the venom’s destructiveness.44 The action mechanism for brown recluse venom is still under investigation. The dermatonecrosis is dependent on both complement and polymorphonuclear leukocytes.‘7.4” In vitro, venom inactivates many of the individual components of human complement. 46-48There is evidence for direct attachment of a component of the venom to the human erythrocyte membrane, making the cells variably susceptible to lysis.45,49-51The degree of attachment to erythrocytes differs by individuals and may be why hemolysis is so variable.49 DIAGNOSIS

Diagnosis of a brown recluse bite can be very difftcult. Spiders that produce lesions similar to those of the brown recluse include those listed in Table 1.52 If the patient does not bring the spider in to the examination, identification of

OF EMERGENCY

TABLE 1.

MEDICINE

Spiders

m Volume

That Produce

8, Number

Lesions

1 n January 1990

Similar

to Those of

L reclusa Acanthoscurria Argiope’ Atrax’ Avicularia Chiracanthium’ Lycosa’ l

Megaphobema Pamphabeteus Phidippus’ Phormictopus Teraphosa Xenesthis

Found in United States.

the specific spider bite is difficult. The lymphocyte transformation test is helpful but not readily available outside of research centers.53 Thus, the diagnosis is usuahy based on a clinically consistent lesion and the known presence of the brown recluse spider in the area. If the diagnosis is suspected in a child, platelets, hemoglobin, and hematocrit should be drawn once a day for 3 days to check for hemolysis. Other laboratory results will remain normal unless the rare complications of disseminated intravascular coagulation or renal failure occur. TREATMENT

Treatment of the brown recluse spider bite should be approached in a systematic way. Most patients are unaware of what bit them and do not come in for treatment until a dermonecrotic lesion is already present. Probably the best treatment for envenomation is antivenom. If administered within the first 24 hours, antivenom would probably significantly decrease the size of the lesions and attenuate the microscopic findings of the dermonecrosis.23.40 Antivenom is not yet commercially available. Conservative treatment for bites with cytotoxic reactions and necrosis remains the best course of treatment. This starts with tetanus prophylaxis and daily wound care. Antibiotics should be used only if cellulitis or another infection occurs. Cool compresses may help alleviate some of the inflammatory reaction. It is difficult to predict which bites will progress to necrotic skin ulcers. The venom appears to be water soluble and spreads through subcutaneous tissues very rapidly.41 Early (within 1 week) surgical debridement with extensive margins and skin grafting has been recommended by several authors.54-56 Rabbit studies and clinical experience show that early excision may not get all of the area ultimately affected and may cause more problems than delayed surgical repair and skin grafting.N,57 Surgery should probably be considered only for necrotic ulcers greater than 1 to 2 cm in diameter. This should be performed only after the borders of the lesion are well established, usually 2 to 3 weeks after the bite.52.57 Intralesion and systemic steroids have had some anecdotal use but are not supported by results of rabbit studies or human series.40.57,58-6’ A more recent therapy is dapsone. In patients who develop a central purplish bleb or vesicle within the first 6 to 8 hours, dapsone may inhibit local infiltration of the wound by polymorphonuclear leukocytes. It shows promise of preventing further necrosis, although as yet there are no large double-blinded studies to prove its efftcacy. Antidotal evidence appears promising for dapsone. One case of a proven bite had resolution of an 8 x 8-cm area of erythema when treated with dapsone within 24 hours.62 One study in the

BLAKE P. GENDRON

n LOXOSCELES

RECLUSA

literature was split among dapsone, dapsone and antivenin, and antivenin without any control patients.63 The authors concluded that the three treatments were equally effective. This is a guarded conclusion pending larger studies that would include control subjects. A recommended dosing schedule would be 50 to 100 mg dapsone once or twice daily. It should be started within 12 hours of the bite. This drug can be toxic. Dapsone should only be used in adults with a proven brown recluse bite; it should not be used in children. One case of methemoglobinemia has been reported.@ Children with severe systemic reactions warrant hospitalization and close observation. If hemolysis occurs, then symptomatic support and packed red-cell transfusion are appropriate. Good hydration and monitoring of renal function are important to insure that hemoglobinemia does not cause renal failure. Systemic steroids, although not of proven efficacy, may be administered in the acute phase (4 to 5 days) in an attempt to stop the destruction of red cells by the venom.65 Loxosceles bites can best be avoided by staying away from spider habitats, including all infrequently used warm, dry areas in the house such as the attic or the insides of furniture. If one is going to work in these areas, gloves and a thin layer of clothing should protect against most bites. Making noise and allowing the spider to leave the area also decreases the possibility of being bitten. REFERENCES 1. Macchiavello A: Cutaneous arachnidism or gangrenous spot in Chile. P R J Public Health Trop Med 1947a;22:425-466 2. Macchiavello A: Cutaneous arachnoidism experimentally produced with the glandular poison of L laeta. P R J Public Health Trop Med 1947b;23:266-279 3. Schmaus LF: Case of arachnoidism (spider bite). JAMA 1929;92:1265-1266 4. Atkins JA, Wingo CW, Soderman WA: Probable cause of necrotic spider bite in the Midwest. Science 1957;126:73 5. Atkins JA, Wingo CW, Soderman WA, et al: Necrotic arachnidism. Am J Trop Med Hyg 1958;7:165-184 6. Gertsh WJ: The spider genus Loxosceles in North America, Central America, and the West Indies. Am Mus Novitates 1958;1907:1-46 7. Anderson PC: What’s new in Loxoscelism? MO Med 1973;70:711-718 8. Majeski JA, Durst GG: Necrotic arachnidism. South Med J 1976;69:887-891 9. Habermehl GG: Venomous Animals and Their Toxins. New York, NY. Springer-Verlag, 1981, pp 33-38 10. Newlands G, lsaacson C, Martindale C: Loxoscelism in the Transvaal South Africa. Trans R Sot Trop Med Hyg 1982;76:610614 11. Efrati P: Bites by Loxosceles spiders in Israel. Toxicon 1969;6:239-241 12. Southcott RV: Spiders of the genus Loxosceles in Australia. Med J Aust 1976;12:406-408 13. Hite JM, Gladney WJ, Lancaster JL, et al: Biology of the brown recluse spider. Agricultural Experiment Station Bulletin 711. University of Arkansas, 1966, pp 1-26 14. Huffoid DC: The brown recluse spider and necrotic arachnidism: A current review. J Arkansas Med Sot 1977;74:126-129 15. Gorham JR: The brown recluse spider and necrotic spider bite. J Environ Sci Health 1968;31:128-145 16. Auer A, Hershey F: Surgery for necrotic bites of the brown spider. Arch Surg 1974:106:612-618 17. Butz W: Envenomation of the brown recluse spider and related species. Clin Toxicol 1971;4:515 18. Huhta V: Loxosceles beta, a venomous spider established

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in a building in Helsinki, Finland, and notes on other synanthropic spiders. Ann Entomol Pennici 1972;38:152-156 19. Demis DJ, Dobson RL, McGuire J: Clin Dermatol 1977; 4:1-8 20. Denny WF, Dillaha CJ, Morgan PN: Hemotoxic effect of Loxosceles reclusa venom. In vivo and in vitro studies. J Lab Clin Med 1964;64:291-298 21. Lessenden CM Jr, Zimmer JK: Brown spider bites: A survey of the current problem. J Kansas Med Sot 1960;61:379-385 22. Keegan HL: Venomous bites and stings in Mississippi. J Miss State Med Assoc 1971 ;13:495-499 23. Russell FE, Waldron WG, Madon MB: Bites of the brown spiders Loxosceles unicolor and Loxosceles arizona in California and Arizona. Toxicon 1969;7:109-117 24. Berger RS: The unremarkable brown recluse spider bite. JAMA 1973;225:1109-1111 25. Wasserman GS, Siegel C: Loxoscelism (brown recluse spider bites): A review of the literature. Clin Toxicol 1973; 14(3):353-358 26. Dillaha CJ, Jansen GT, Honeycutt WM, et al: North American loxoscelism. JAMA 1964;188:33-36 27. Anderson RC: Treatment of severe loxoscelism. MO Med 1971;70:711-718 28. Foil LD, Norment BR: Envenomation by Loxosceles reclusa. J Med Entomol 1979;16:211-218 29. Butz WC, Stacy LD, Heyford NN: Arachnidism in rabbits. Arch Pathol Lab Med 1971;91:97-100 30. Duffy PH, Limbacker HP: Brown spider bites in Arizona. Ariz Med 1971;28:89-95 31. Dillaha CJ, Jensen GT, Honeycutt WM, et al: The gangrenous bite of the brown recluse spider in Arkansas. J Arkansas Med Sot 1963;60:91-94 32. Micks DW: The current status of necrotic arachnidism in Texas. In Keegan JL, MacFarlane WV (eds): Venomous and Poisonous Animals and Noxious Plants of the Pacific region. Elmsford, NY, Pergamon, 1963, pp 153-157 33. Forrester LJ, Barrett JT, Campbell BJ: Red blood cell lysis induced by the venom of the brown recluse spider: The role of sphingomyelinase D. Arch Biochem Biophys 1978;187:355 34. Madrigal GC, et al: Toxicity from the bite of the brown spider. Clin Pediatr (Phila) 1971 ;11:641-644 35. Minton SA, Ofson C: A case of spider bite with severe hemolvtic reaction. Pediatrics 1969:33:283-287 36. Verse H, et al: Desseminated.intravascular coagulopathy following fatal brown spider bite. J Pediatr 1972;80:1035-1037 37. Abildgaard CF: Recognition and treatment of intravascular coagulation. J Pediatr 1969;74:163 38. Smith CW, Micks DW: The role of polymorphonuclear leukocytes in the lesion caused by the venom of the brown spider, Loxosceles reclusa. Lab Invest 1970;22:90-93 39. Jong YS, Norment BR, Heitz JR: Separation and characterization of venom components in the brown recluse spider. II-Piolease activity. Toxicon 1979;17:529-537 40. Rees R, et al: Management of the brown recluse spider bite. Plast Reconstr Surg 1981;68(5):768-773 41. Geren CR, et al: Isolation and characterization of toxins from brown recluse spider venom. Arch Biochem Biophys 1976;174:90 42. Wright RP, Elgert KD, Campbell BJ, et al: Hyaluronidase and esterase activities of the venom of the poisonous brown recluse spider. Arch Biochem Biophys 1973;159:415 43. Wright RP: Enzymic characterization of brown recluse spider venom. Bull MO Acad Sci 1973;2:94 44. Babcock JL, Marmer DJ, Steele RW: lmmunotoxicology of brown recluse spider venom. Toxicon 1986;24:783-790 45. Futrel JM: An in vitro model for studying hemolysis associated with venom from the brown recluse spider. Toxicon 1979;17:354-361 46. Futrel JM, Morgan PN: Inhibition of human complement components by Loxosceles reclusa venom. Int Arch Allergy Appl lmmunol 1978;57:275-278 47. Kniker WT, Morgan PN: An inactivator in spider venom of the fifth component of complement (~‘5). Fed Proc 1967;26:362 48. Kniker WT, et al: An inhibitor of complement in the venom

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of the brown recluse spider, L. reclusa. Proc Sot Exp Biol Med 1969;131:1432-1434 49. Futrel JM, et al: Localization of brown recluse venom attachment sites on human ervthrocvtes bv the ferritin labeled antibody technique. Am J Pathol 1979;95:675-662 50. Nicholson JF, Nicholson BH: Hemolytic anemia from brown recluse spider. South Med J 1962;59:1209-1211 51. Morgan BB, et al: Lysis of human erythrocytes by venom from the brown recluse spider, L. reclusa. Toxicon 1976;16:6566 52. Wasserman GS, Anderson PC: Loxoscelism and necrotic arachnidism. J. Toxicol Clin Toxicol 1964;21:451-472 53. Finke JH, et al: Serodiagnostic test for Loxosceles reclusa bites. J Med Entomol 1974;16:211-261 54. Arnold RE: Brown recluse spider bites: Five cases with a review of the literature. J Am Coll Emerg Phys 1976;5:262-264 55. Fardon DW, et al: The treatment of the-brown spider bite. Plast Reconstr Surg 1967;40:482-488 56. Schenone H, Pratts F: Arachnidism by Loxosceles laetaForty cases. Arch Dermatol 1961;83:139 57. Rees RS, Altenbern DP, Lynch JB, et al: Brown recluse

spider bites: A comparison of early surgical excision versus dapsone and delayed surgical excision. Ann Surg 1965;202:659-663 56. Anderson PC: The brown recluse spider bite: New problems, new theraov. J Ind State Med Assoc 1976:71:681-663 59. Chu J, et’al: Hemolytic anemia following brown spider bite. Clin Toxicol 1978;12:531-534 60. Jansen GT, et al: The brown recluse spider bite: Controlled evaluation of treatment using the white rabbit as an animal model. South Med J 1971;64:1194-1202 61. Mara JE, et al: Brown spider bite-Treatment with hydrocortisone. Rocky Mount Med J 1977;257-258 62. King LE, and Rees RS: Dapsone treatment of a brown recluse bite. JAMA 1983;250:648 63. Rees P, Campbell D, Rieger E, et al: The diagnosis and treatment of brown recluse spider bites. Ann Emerg Med 1987;16:945-949 64. lserson K, Methemoglobinemia from dapsone therapy for a suspected brown spider bite. J Emerg Med 1985;3:285-288 65. Rees RS, Nanney LB, Yates RA, et al: Interaction of brown recluse spider venom on cell membranes: The Inciting Mechanism. J Invest Dermatol 1985;83:270-275