Chapter 52 Spider Bites
Spiders and Their Venoms
Spiders number nearly 42,000 described species and are found in all habitats except the open sea.38,64,225,227 They are carnivorous predators with important ecologic roles in most terrestrial ecosystems. Many are capable of wind-borne dispersal (ballooning), which has led to colonization of even the most isolated land masses on Earth.
As with ticks, mites, scorpions, and other arachnids, the spider’s body consists of an abdomen and an unsegmented cephalothorax (prosoma) with chelicerate jaws, pedipalps, and four pairs of legs (Figure 52-1). They are distinct from other arachnids in that they have no abdominal segmentation and the male pedipalpal tarsi are modified as secondary genitalia.273 In addition, spiders have venom that is produced in a gland in the anterior prosoma (Figure 52-2) and delivered through a cheliceral fang. On the abdomen, they have silk-producing glands and a set of spinnerets.
The overwhelming majority of spider species is carnivorous, so eating involves the challenge of capturing live prey. Prey capture is a multistep process in which spiders must find prey, ensnare it, immobilize it, and digest it externally before the liquefied meal can be consumed. Venoms are a central tool in this process, and the primary function of venom in spiders is prey capture. They are also, but more rarely, used in defense. For their predatory function, venoms are complex mixtures of neurotoxic and proteolytic peptides, proteins, and biogenic amines.1,15,107,202,273 The venom of a single spider can have between 200 and 1000 distinct chemicals.89 In the past decade there has been a burst of research interest in spider venoms because they contain vast stores of unknown chemical compounds with potential application in research, pharmacology, or as insecticides. We direct the curious to Arachnoserver,336 a database of sequences, structural, and molecular target information of all published spider venom toxins.
Transcriptomic and proteomic analyses are beginning to reveal patterns of complexity and variation in venom composition within and among species. We do not attempt to review the full literature of characteristics of spider venoms, but rather focus on what is known (and unknown) about venoms and their effects on humans. Most toxins in spider venoms have great target specificity, acting selectively on arthropods, vertebrates, or other groups, including some with mammalian-specific activity.1,126,221 Venom composition varies widely across spider species, and variation may exist within species between genders and among geographically isolated populations.136,200 Venom potency also varies within individuals, both seasonally and developmentally. Despite this tremendous venom diversity, only a few dozen spider lineages are considered harmful to humans because (1) most others have an insufficient quantity of venom, (2) the toxins do not affect mammals, or (3) the fangs cannot penetrate human skin. In a few species, although laboratory evidence suggests potential mammalian toxicity, human envenomations have not been reported, perhaps because of the rarity of encounters between spiders and humans in some habitats. Table 52-1 lists an assortment of spider families, including those with species that have been reported to bite humans.
General Assessment and Treatment of Spider Bites
Awareness of the differential diagnosis is crucial for management of any patient presenting for evaluation of “spider bite,” because the offending creature is rarely observed and identified. In general, it is outside of normal biologic activity for spiders to bite humans, except in defense. A defensive bite risks the spider’s life and tends to occur only when its life is threatened by being crushed. Thus, true spider bites are much less common causes of skin lesions than are insect bites or cutaneous infections. Furthermore, no pathognomonic clinical signs prove the diagnosis without retrieval and identification of a spider that was seen actually biting.254 Diagnosis of arachnidism without direct evidence can lead to inappropriate treatment and inadequate consideration of more severe underlying medical issues.162,165,168,247,296 Therefore, the medical history, physical examination, and laboratory evaluation of putative spider bites must usually take into consideration an alternative etiology. Treatment plans should include careful follow-up and patient counseling to manage any uncertainties in the final diagnosis.
Guide to Spider Diversity and Identification
This chapter provides more information on spider diversity than do most reviews in order to (1) inform the reader of the immense diversity of spiders that are medically insignificant and thus emphasize the rarity of spiders known to cause medical problems; (2) emphasize the need for accurate species identification, particularly in reporting of cases for publication or teaching; and (3) facilitate accurate identification of spiders that are caught in the act of biting by directing professionals to proper identification keys. Table 52-1 includes species worldwide that are currently known or suspected to be medically noteworthy, even minimally, either through the effect of bites or urticating hairs. Geographic range and the most recent systematic work on each group are included. Box 52-1 lists the genera of serious medical significance for each continent. For effective communication, groups of spiders must be recognized by the same name worldwide. This chapter uses the current official nomenclature.
Of the three spider suborders, two contain clinically significant species: Mygalomorphae and Araneomorphae. Mygalomorphs include the baboon spiders or tarantulas, trapdoor spiders, purse-web spiders, mygalomorph funnel-web spiders, and several other groups that lack common names. Most spiders are araneomorphs. These include jumping spiders, orb-weaving spiders, widow spiders, wolf spiders, and fiddleback spiders (see Table 52-1). The most conspicuous characteristics that distinguish these groups are the orientation of the chelicerae (jaws) and the number of book lungs. Spider fangs are located on the chelicerae, which open sideways in the Araneomorphae and move diagonally in the Mygalomorphae, requiring the latter to rear back for a downward, snakelike strike (Figures 52-3 and 52-4). Mygalomorphae have two pairs of book lungs, whereas most Araneomorphae have only one pair. Lung slits, which open into the book lungs, are easily visible in a ventral view of the anterior abdomen (see Figure 52-1). Characteristics that distinguish families, genera, and species include eye number and pattern, numbers of tarsal claws, and details of genitalia structure.
FIGURE 52-3 Movement of the chelicerae in mygalomorphs (A) and araneomorphs (B).
(Modified from Foelix RF: Biology of Spiders, ed 2, Oxford, UK, 1996, Oxford University Press. With permission.)
FIGURE 52-4 Fangs of mature male tarantula (Aphonopelma species).
(Courtesy Michael Cardwell and Associates, 1992.)
Although many spider species are geographically localized (e.g., Atrax robustus in Australia, Phoneutria nigriventer in Brazil), some, such as the widow spiders (Latrodectus), are found worldwide (see Table 52-1). Others, such as members of the Loxosceles genus, are widely distributed in more than one continent, and still others, such as Tegenaria agrestis, appear to have naturalized in specific geographic regions distant from their point of ecological origin. Because of the resulting worldwide species diversity and overlap, the remainder of this chapter is structured according to spider taxonomy rather than isolated species or geographic location.
Suborder Mygalomorphae
Family Theraphosidae: Tarantulas and Baboon Spiders
Theraphosidae is the largest mygalomorph family with respect to both numbers of species and sizes of the largest individuals (Figure 52-5). Approximately 800 described species are found on all continents, with the greatest abundance and diversity in tropical regions. They mature in 3 to 9 years and can live for 15 to 25 years. Individuals live in burrows, with trip-line threads extending from the entrance. These are sometimes located in abandoned rodent burrows or hollow trees. Theraphosids have dense tufts of specialized hairs on their tarsi (feet) that enable them to climb on smooth surfaces and may aid in prey capture. They have two tarsal claws, eight closely grouped eyes, and two pairs of spinnerets. As a group, they are found mainly in tropical and subtropical areas.
Grammostola mollicoma is the largest tarantula known, with a body length of 7 to 10 cm (3 to 4 inches) and leg spread of 21 to 27 cm (8.3 to 10.6 inches).42,111 Harpactirella lightfooti, the baboon spider or bobbejaan-spinnekop, is a mygalomorph spider found in South Africa. Body length is 3 cm (1.2 inches); the cephalothorax is brown with a yellowish border.
Venom
In the last few years our understanding of tarantula venoms has increased because of analyses of the venom transcriptomes and proteomes of multiple species.157 In the United States, Rheochostica henzi and members of the genus Aphonopelma (Figure 52-6) have venom containing hyaluronidase, nucleotides, and polyamines.48,58,172,259,260 Polyamines are thought to act as neurotransmitters and increase venom effectiveness, particularly with respect to paralysis of insect prey.273 Hyaluronidase is postulated to be a spreading factor, and the nucleotide adenosine triphosphate (ATP) potentiates the major effects of the venom on mice. Both venoms cause rapid, irreversible necrosis of skeletal muscle when injected intraperitoneally into mice.223 Dugesiella (Rheochostica) venom was found to have a necrotoxin with several similarities to sea snake venoms.172 In comparison, the venom of Scodra griseipes, an African tarantula, includes higher-molecular-weight (greater than 25,000 daltons) proteins and enzymes plus lower-weight polypeptides (4000 to 9000 daltons); the second group is believed to contain polypeptide neurotoxins.56 S. griseipes venom toxins have an effect on mammalians, but this species is not known to be clinically relevant. Recent work suggests that venom chemotaxonomy may be a useful method of nondestructive species recognition, at least within the Brachypelma genus.88
Urticating Hairs
Several genera of tarantulas, including Haplopelma, Lasiodora, Grammostola, Acanthoscurria, and Brachypelma, possess urticating hairs irritating to skin and mucous membranes. These genera are located throughout the western hemisphere, with many species indigenous to the United States. When one of these spiders is threatened, it rubs its hind legs across the dorsal surface of its abdomen and flicks thousands of hairs toward the aggressor. These barbed hairs can penetrate human skin, causing edematous, pruritic papules. Itching may persist for weeks. There are four morphologic types of urticating hairs. Tarantulas within the United States possess only type I hairs, which do not penetrate the skin as deeply as do type III hairs. Type II hairs are incorporated into the silk web retreat and are not thrown off by the spider. Type III hairs can penetrate up to 2 mm into human skin; this is the type of hair most likely to cause inflammation. They are typically found on Mexican, Caribbean, and Central and South American species. Type IV hairs, which belong to the South American spider Grammostola, are able to cause inflammation of the respiratory tract in small mammals. Rats and mice have been reported to die of asphyxia within two hours after exposure to the hairs.67,328
Clinical Presentation
Despite the presence in venom of components toxic to rodent nerves and skeletal muscle, most tarantula bites result in only mild to moderate local symptoms in humans. A few can cause more severe pain and swelling, numbness, or lymphangitis. In a series of nine cases in Australia, by either Selenocosmia species or Phlogiellus species, no major effects occurred. Local pain was the most common effect, followed by puncture marks or bleeding. Severe pain occurred in four of seven patients, where severity of pain was documented. Mild systemic effects occurred in one case.149 Species of tarantula implicated as causes of human envenomation include those in genera Mygalarachne (formerly Sericopelma) of Panama, Pterinochilus of Africa, Aphonopelma of Mexico and the United States, Pamphobaeteus of South America, Euathlus of Costa Rica, Theraphosa of French Guyana, Grammostola of Colombia, Selenocosmia and Phlogiellus of Australia, Poecilotheria of India, Lampropelma of Thailand, Lasiodora of Brazil, and Avicularia of Central America and the southwestern United States. Envenomation usually involves immediate pain at the bite site, occasionally followed by some redness and swelling, and is usually without necrosis or serious sequelae.42,48,58,109,260
A paucity of reports in the peer-reviewed medical literature hinders proper characterization of occasional tarantula neurotoxicity, particularly in cases (e.g., Poecilotheria) that are reported anecdotally and in the pet trade, to provoke severe neuromuscular symptoms Although no fatalities have been reported, localized pain followed by emesis, weakness, and collapse have been noted after envenomation by Harpactirella lightfooti, the baboon spider of South Africa.42,129,213
Urticating hairs may cause intense inflammation, which may cause pruritus for weeks. Individuals who handle tarantulas may unwittingly transfer urticating hairs from hand to eye, causing keratoconjunctivitis or ophthalmia nodosa. Keratoconjunctivitis has been described after handling of a Thailand black tarantula, Haplopelma minax. Fine intracorneal hairs were noted at examination, and inflammation settled quickly with topical corticosteroid treatment; at a 36-month follow-up, the eye was normal.37
More severe ophthalmic complications occurred in two cases after handling Chilean rose tarantulas, Grammostola cala. In these victims, initial findings were similar, with intracorneal hairs and keratoconjunctivitis, but progressive panuveitis followed, with corneal granulomas, iritis, cataract, hyalitis, and chorioretinitis apparently related to migration of hairs through the media of the eye. The differences in outcome with exposure to the two species may result from differences in hair morphology, which may also explain differences in other reports of ophthalmic injury from tarantula or caterpillar hair exposure.37 Similar cases of ophthalmia nodosa have been described.24,171 Sheth and colleagues,268 in London, reported another case of ocular inflammation after handling a pet Chilean rose tarantula. A 9-year-old boy presented with new onset of painful red right eye, initially thought to be trauma-induced 2 weeks earlier. The left eye was unaffected and visual acuity was within normal limits. Slit-lamp examination showed right eye injection with multiple hairs at all levels of the cornea with associated opacities, and moderate anterior uveitis. In addition, hair-like vitreous lesions and peripheral full-thickness retinal infiltrates were seen. Topical therapy with corticosteroids and antibiotics was initiated and follow-up continued with long-term tapering topical steroids. Hair removal was not attempted because of the large number and depth of hairs. Eighteen-month follow-up revealed full resolution of inflammation, normal visual acuity, and no complications (Figures 52-7 and 52-8).
FIGURE 52-7 Cornea showing multiple tarantula hairs with associated inflammatory infiltrate and scarring.
(From Atkins JA, Wingo CW, Sodeman WA, et al: Necrotic arachnidism, Am J Trop Med Hyg 7:165, 1958.)
Family Hexathelidae: Funnel-Web Mygalomorphs
The family Hexathelidae includes 11 genera and approximately 74 species, which are currently known from the Old World and Chile.237 The funnel webs that typify members of this group are silk-lined tubular retreats that extend into a protected space, such as a burrow in the ground or a hole in a tree. Sheets of silk radiate from the retreat and signal the presence of prey. These webs superficially resemble webs of araneomorph spiders in the family Agelenidae. Distinguishing characteristics of the spiders include a shiny carapace; long, spiny sensory hairs on the legs; and paired claws lacking claw tufts on the tips of the feet, with teeth lining the medial claw.
Clinically significant hexathelid spiders are species of Atrax (Figure 52-9) and Hadronyche. Technically, taxonomists now consider Atrax and Hadronyche species as members of only one genus.237 To avoid confusion in the literature, species names still use either Atrax or Hadronyche, depending on their original names. We discuss these species as a cohesive taxonomic group. Among these, the species A. robustus is best known and most carefully studied. Atrax and Hadronyche species, all of which are believed to be dangerous, have been described in southern and southeastern Australia, Tasmania, Papua New Guinea, and the Solomon Islands. As a group, they prefer cool, moist coastal and mountainous regions.122,124,269
FIGURE 52-9 Funnel-web spider (Atrax species) wearing an engagement ring.
(Courtesy Sherman Minton, MD.)
Genus Atrax/Hadronyche
Biology
Funnel-web spiders have a glossy ebony cephalothorax and velvety black abdomen. The abdominal undersurface may have brushes of red hair. The fangs reach 4 to 5 mm (0.16 to 0.19 inch) in length and are capable of penetrating a fingernail or a chicken’s skull, sometimes making removal of the spider difficult. Females are somewhat larger than males, with a body length of 4 cm (1.57 inches). Mature males are more delicate, with a tibial spur on the second pair of legs and pointed pedipalps.146,262
A. robustus, the Sydney funnel-web spider, is limited to a 160-km (100-mile) range around the center of Sydney, Australia. The spider creates a tubular or funnel-shaped, silk-lined shallow burrow under rocks, logs, fences, stumps, or thick vegetation or around foundations of houses. Colonies of up to 150 spiders have been found. Females rarely roam far from their webs; males live a vagrant life after reaching maturity. Wandering males may enter houses or other areas of human habitation, especially during the summer months after a heavy rain. Its aggressive behavior and potent venom make the male Sydney funnel-web arachnid one of the most dangerous spiders in the world. It is responsible for all known fatal Atrax envenomations.2,127,262,294
H. formidabilis, the northern funnel-web spider, is found in the central coastal region of New South Wales and the adjacent Blue Mountains. Its tree-dwelling habit was once thought to be unique, but it is now known that other species also live in trees. The webs may be camouflaged in rough-barked trees, such as melaleuca (paper bark), banksia, and eucalyptus.124
Venom
Although many species have venom with significant in vitro toxicity, few have been implicated in human illness. The best described of these is A. robustus. Atrax venom causes widespread release of neurotransmitters.81,124,132,276,282 This may occur by a direct action of the venom on nerve membranes, producing spontaneous action potentials and consequently provoking a global outpouring of transmitters that accounts for the neuromotor and autonomic stimulation seen clinically.
Early efforts to purify the active component of Atrax venom resulted in reports of neurotoxins of various molecular weights purified from venom preparations in separate experiments.281 These were termed atraxotoxin (10,000 to 25,000 daltons, from milked venom),124 robustoxin (4887 daltons, also from milked venom),270 and atraxin (9800 daltons, from ground venom glands).125 Venoms of A. robustus, H. cereberea, H. formidabilis, H. infensa, H. lanunstian, H. variela, H. versula, and an Atrax species preparation and Hadronyche species preparation have similar high- and low-molecular-weight protein electrophoretic patterns and Western blotting, suggesting that all of these species contain similar atraxotoxins. The relationships among these toxins are not clear, but atraxotoxin or atraxin may be a precursor to robustoxin. In addition to these components, Atrax venom contains various lower-molecular-weight compounds, including citric acid, lactic acid, phosphoric acid, glycerol, urea, glucose, γ-aminolevulinic acid, glycine, spermidine, spermine, tyramine, octopamine, and 5-methoxytryptamine.80
The best characterized of the toxins is robustoxin, whose 42–amino acid sequence was determined in 1985.270 It is the sole lethal toxin that can be isolated by cation-exchange chromatography, and its effects in monkeys duplicate the effects of crude venom preparations. A 5 mg/kg intravenous (IV) dose of robustoxin to monkeys causes dyspnea, blood pressure fluctuations culminating in severe hypotension, lacrimation, salivation, skeletal muscle fasciculation, and death within 3 to 4 hours of administration.209
Isolated human intercostal muscles were studied to determine the etiology of muscle fasciculations. Muscles treated with A. robustus venom developed marked contractions, which were abolished by d-tubocurarine.51 Muscles treated with venom for more than an hour stopped contracting and could be stimulated only by increasing the stimulus duration. A. robustus venom has been shown to lack anticholinesterase activity.280 Contractions are not a direct venom action on the muscle fiber, so acetylcholine appears to have been released from the presynaptic terminals.102 Muscle fasciculations are apparently caused by abnormal repetitive firing of motor neurons. It was hypothesized that the venom changes the membrane’s electric field, activating sodium channels without altering the transmembrane potential or damaging the neuronal membrane ultrastructurally.81,124,276
The initial hypertension in Atrax toxicity may have several causes. Morgans and Carroll204,205 demonstrated direct α-adrenergic stimulation with vasoconstriction of isolated arterial preparations exposed to A. robustus venom. In rabbit atria, an initial decrease followed by an increase in cardiac inotropy and chronotropy may result from vagal acetylcholine and myocardial norepinephrine releases, respectively.52 The combination of myocardial responses and peripheral vasoconstriction may explain the initial hypertensive response.
Animal species vary in susceptibility to Atrax venom. Rabbits given 15 mg of crude venom intravenously and cane toads given 12 mg of female Atrax venom show no effects after envenomation. Primates, including humans, are among the most susceptible species. Newborn mice, also highly susceptible, have been used as an in vivo biologic assay for venom toxicity.124,285 Sutherland287 found that a lethal dose of venom from a male A. robustus could be neutralized in newborn mice by nonimmune sera from rabbits and other nonprimate vertebrates. Sheumack and co-workers271 later demonstrated that the active fraction of nonimmune rabbit sera contained immunoglobulins G and M (IgG, IgM).
In addition, venom potency varies with time of year, recent feeding history, maturation, and gender of the individual spider.12 Between 1956 and 1963, Wiener330 demonstrated significant differences in the venoms of male and female Atrax spiders. Males had an average venom yield of 1.01 mg, less than the 1.84 mg average yield from females. On the other hand, guinea pig lethality was much greater after a bite by a male (75% to 90%) than by a female spider (20%). Weiner concluded that significant qualitative difference exists between the venoms of males and females.
Monkeys, which have a pattern of envenomation similar to that in humans, provide a model in which Sutherland285,291 has described a biphasic clinical syndrome. Phase I begins minutes after venom injection, with local piloerection and muscle fasciculation. This extends proximally, becoming generalized over the next 10 to 20 minutes. After another 5 minutes, severe hypertension, tachycardia, hyperthermia, and coma with increased intracranial pressure may occur, followed by diaphoresis, salivation, lacrimation, diarrhea, sporadic apnea, borborygmi, and grotesque muscle writhing. Death may result from asphyxia caused by laryngeal spasm, combined with copious respiratory secretions, apnea, or pulmonary edema. Laboratory evaluation reveals metabolic acidosis and elevated plasma creatine phosphokinase. Phase II begins 1 to 2 hours after envenomation as the phase I symptoms subside. The victim may return to consciousness and appear to recover. In severe cases, hypotension gradually worsens over 1 to 2 hours, with periods of apnea. Pulmonary edema and death may occur despite ventilatory support.
Clinical Presentation
Up to 90% of Atrax bites may not result in significant envenomation.328 Intense pain at the bite site may result from direct trauma as well as the venom’s effect, but the bite does not provoke cutaneous necrosis. Wiener330 studied the cutaneous effects of the venom on himself by injecting 0.5 mg intradermally. Local pain and a wheal surrounded by erythema lasted for 30 minutes, followed by localized sweating and piloerection. No systemic effects occurred.
One case of cutaneous necrosis has been reported. Nayar and colleagues211 described a man visiting in New Zealand and reportedly bitten by a funnel-web spider when reaching into a bag of onions purchased at a shop. On return to England, he was treated at a hospital on two occasions with incisions and drainages for suspected infection of his thumb tip. Subsequently, his thumb became necrotic, with eventual osteocutaneous necrosis extending to the mid-terminal phalanx. Surgical treatment consisted of a Moberg flap reconstruction. No systemic involvement was seen, and he eventually returned to work.
The earliest systemic signs and symptoms may include perioral tingling, nausea and vomiting, diaphoresis, salivation, lacrimation, and dyspnea. Pulmonary edema follows, along with a generalized central and peripheral neurologic syndrome that includes muscle fasciculations, tremor, spasms, weakness, and impaired consciousness. Death may occur secondary to pulmonary failure, hypotension, or cardiac arrest.282,328
Thirteen fatalities from A. robustus envenomation were recorded between 1927 and 1984. Children are particularly susceptible; those younger than 12 years of age may die within 4 hours of the bite.97,133,288 Before the development of specific antivenom in 1980, severe envenomations resulted in a minimum 8-hour critical period, followed by a 9- to 21-day hospital course.96,288,291
No fatalities caused by H. formidabilis have been recorded, although several severe envenomations have occurred.124 Venoms of A. robustus, A. versutus, A. infensus, and A. formidabilis appear to have comparable vertebrate toxicity in vitro.11
Treatment
Immediate treatment after a bite is modeled after that for Australian snakebite and consists of four steps: (1) wrap the length of the bitten extremity with an elastic bandage, (2) splint to immobilize the extremity, (3) immobilize the victim, and (4) transport to the nearest hospital with the bandage in place.220,289 A human case report has illustrated utility of this method, with occurrence, disappearance, recurrence, and re-resolution of symptoms coinciding with compression wrap removal and replacement in a man bitten by a male A. robustus.118 An experimental model in Macaca fascicularis monkeys has supported efficacy of the pressure immobilization technique.284,285,292
Specific antivenom has been the mainstay of treatment for Atrax envenomation since 1981. The antivenom is a purified IgG product developed by Sutherland and associates286,293 at the Commonwealth Serum Laboratories by immunizing rabbits with a combination of male Atrax venom and Freund’s adjuvant. The antivenom was demonstrated to neutralize Atrax venom in vitro and to reverse symptoms in monkeys before its introduction for human use. It has been used with good effect in humans bitten by Atrax and Hadronyche species.75,291
If a tourniquet or bandage is in place when the victim presents for hospital care, an IV line should be initiated before removing the tourniquet or bandage in an intensive care setting, with careful observation for development or progression of symptoms. If systemic signs or symptoms occur, victims are usually treated with antivenom administration. Two ampules of antivenom (100 mg of purified IgG per ampule) are administered intravenously every 15 minutes until symptoms improve. Dosing is the same for children as for adults, and total doses of two to eight ampules have been reported. During a 10-year period, antivenom was given to at least 40 persons, with no adverse effects or deaths reported.291
Other than antivenom, no consistently effective agent has been found to enhance survival after Atrax envenomation. Diazepam, atropine, and furosemide have been found to increase survival in monkeys, but this may not be the case in humans.95,139
Sheumack and colleagues272 developed a toxoid from robustoxin by polymerization with glutaraldehyde. Immunization with the toxoid conferred protection against the lethal effects of 50 mg/kg Atrax venom in monkeys for at least 26 weeks after toxoid injection.
Family Actinopodidae
Genus Missulena: Mouse Spiders
Venom
Missulena venoms have recently been confirmed to have a major bioactive component, δ-missulenatoxin-Mb1a,128 that is homologous to the δ-atraxotoxins of atraxine spiders (see earlier text). This toxin has strong insecticidal potency and acts by manipulation of tetrodotoxin-sensitive sodium channels. The discovery of this toxin and its homology with atraxotoxins indicate extreme conservation of this toxin family.128 This finding also provides a mechanistic explanation for observed similarities between the toxic effects of bites of Missulena bradleyi and those of Atracines in animals.236
Clinical Presentation
In a series of 13 envenomations, pain was the most common complaint, severe in 10, with puncture marks, bleeding, redness, and edema being the next most common complaints. Three patients exhibited neurotoxic effects; all three exhibited paresthesias, one with accompanying diaphoresis. Nonspecific systemic effects occurred in five patients. There were no cases of severe envenomation in this series. There has been a total of 40 reported Missulena bites, with one case of severe envenomation. This occurred in a 19-month-old child in Queensland.148,154
Treatment
Treatment is largely symptomatic and supportive. In the case of severe envenomation of the 19-month-old child, administration of funnel-web spider antivenom, raised against male A. robustus venom, produced dramatic improvement in her condition, with full recovery following a second dose.236 Although severe envenomation is rare, it is suggested that all suspected Mygalomorphae bites be observed for 4 hours to exclude such envenomation.148,154
Dipluridae, Genus Trechona
Biology
Trechona venosa is a large South American funnel-web tarantula with neurotoxic venom potentially dangerous to humans.42,109,129 As with all Trechona species, T. venosa is sedentary, living in holes or on plants in tropical forests along the Atlantic coast. The spider may be black or gray-brown with yellow stripes on the abdomen. Mature body length may be 3 to 4.5 cm (1.2 to 1.8 inches), with 6- to 7-cm (2.4- to 2.8-inch) legs and 3- to 4-mm (0.12- to 0.16-inch) fangs. T. venosa is not found in Chile, but in this region it has been confused, particularly in venom studies, with a spider in the family Nemesiidae, Acanthogonatus subcalpeianus, which it resembles.237
Venom
The venom of T. venosa is extremely toxic to rats, with an apparent action similar to that of Phoneutria species.186 Little is known about venom composition.
Suborder Araneomorphae
Enormous diversity is found within the group Araneomorphae, which contains more than 85% of the approximately 42,000 currently described spider species.64,231,326 Araneomorphs, or true spiders, are found throughout the world in all terrestrial (and a few aquatic) habitats. They show tremendous variability in size, appearance, and habit; however, no araneomorphs are as large as the largest tarantulas. Characteristics that distinguish araneomorphs include features of the spinnerets that enable them to produce extremely sticky silk. All but a few groups have only one pair of book lungs. Most have eight eyes, but eye number varies from two to eight. Prey capture tactics usually determine where a spider will be found and are generally consistent within particular groups. Thus, these tactics often provide conspicuous clues that help identify spiders.
Family Sicariidae: Recluse Spiders
Sicariidae includes two genera, Loxosceles and Sicarius, both of which are clinically important. The family falls within a larger group of families (Scytodoids) that all have only six eyes. In these two genera, the eyes are in dyad pairs. The chelicerae are fused at the base, and the labium is fused to the sternum. Males have more slender abdomens and more prominent pedipalps than do females. Previously, Loxosceles was placed in its own family, Loxoscelidae, but this was recently synonymized with Sicariidae.229
Genus Loxosceles: Brown or Fiddle Spiders
Biology
Loxosceles, commonly known as brown or fiddle spiders, build small, irregular, and sticky webs in small areas, such as under rocks or wood or in human-made habitats. The genus contains more than 100 species, with centers of diversity in North or South America and Africa.20,79,192,256,264 These spiders are 8 to 15 mm (0.3 to 1.6 inches) in adult body length, are light to dark brown, and have a dark, violin-shaped spot centered anterodorsally, such that the neck of the fiddle extends toward the posterior end of the cephalothorax. The shape and darkness of the fiddle, relative lengths of the first two pairs of legs, and genitalia characteristics are features that help distinguish species45,142,264 (Figure 52-10).
FIGURE 52-10 Adult female desert violin spider (Loxosceles deserta).
(Courtesy Michael Cardwell and Associates, 1994.)
From the South American Loxosceles laeta to the South African L. spinulosa, these small arachnids have been associated with human pathologic conditions. Several species have been associated with necrotic arachnidism in the United States: L. reclusa (the true brown recluse spider, Figure 52-11), L. rufescens, L. arizonica, and L. laeta. These spiders are native to all the southernmost states. In the Mississippi River Valley, their territory extends as far north as southern Wisconsin. Species native to one region or habitat may adapt successfully to new locations after transport by humans.216,322
FIGURE 52-11 Brown recluse spider. A, Loxosceles reclusa. B, Loxosceles vonwredei, a cave-dwelling species from Namibia.
(A courtesy Indiana University Medical Center; B courtesy Greta J. Binford.)
Brown spiders regularly roam in search of new web sites, and males wander in search of females. They are most active at night from spring through fall, emerging from rock piles, woodpiles, and rats’ nests to hunt insects and other spiders. South African savanna species have been observed under stones and logs and in the tunnels of old termite nests; spelean species are found naturally in caves but have also appeared in homes and export warehouses.212,215,218 Brown spiders may infest homes, generally preferring warm, undisturbed environments, such as vacant buildings and storage sheds. In Chile, the tendency to inhabit human dwellings has earned L. laeta the names araña de los rincones (corner spider) and araña de detrás de los cuadros (spider behind the pictures).265 Loxosceles distributions are patchy, but when they are present they can reach high densities. For example, 2055 individual L. reclusa were captured in a single-family home in Kansas in a 6-month period.318 Molts, or shed exoskeletons, are good indicators of the presence of resident Loxosceles. Webs are small, flocculent structures made in crevices with a bluish tint in bright light. Egg sacs are laid flat against surfaces, typically with a layer of fluffy silk on the exposed surface. Females may live 1 to 3 years, and longer in captivity.109,143 Naturally unaggressive toward humans, brown spiders are not prone to bite unless threatened or trapped against the skin. Bites typically follow retrieval of old bed sheets or jackets from storage. Thorough housecleaning with movement of boxes and stored items at least once per year highly reduces the likelihood of establishment of robust populations of Loxosceles in houses.110
A study by Vetter319 showed that of 1773 spiders thought to be L. reclusa by medical professionals, only 324 actually were Loxosceles. In addition, the true recluses were from regions historically known to be in their home range. Only one brown recluse spider was found outside the normal habitat region, and this case was explained by recent travel. Of the other 1449 submissions that were spiders, more than 38 families, 88 genera, and 158 species were identified. It was noted that more accurate identification occurred in areas with known historical populations. This study also suggests that the brown recluse has not migrated throughout the United States, but remains within its home regions.
Venom
Fractionated Loxosceles venom contains at least eight or nine major protein bands and three or four minor bands identifiable by 1-D protein gel electrophoresis36,242 and hundreds of proteins identifiable by 2-D gel electrophoresis.33a Recent proteomic and transcriptomic analyses have identified a minimum of 400 distinct toxic components in venoms of South American Loxosceles.93 Hyaluronidase was first identified as a component by Wright and associates.337 Hyaluronidase probably plays a facilitating role in lesion development, encouraging the spread of other venom components; however, it is not itself a cytotoxin. Hydrolytic enzyme activities include esterase,337 alkaline phosphatase,135 lipase,159 5′-ribonucleotide phosphorylase,108 and astacins302 but none of these alone appears to explain cytotoxicity.
Sphingomyelinase D, a 32- to 35-kDa venom protein family, is the sufficient causative agent for formation of dermonecrotic lesions following Loxosceles bites.169,297,299 Homologs of sphingomyelinase D constitute up to 18% of the proteins in Loxosceles venom.93 The sphingomyelinase D enzyme activity is rare in nature and is currently only known elsewhere in tick saliva and as an exotoxin of pathogenic bacteria. Sphingomyelinase D is present in L. intermedia spiderlings starting with the third instar, with increasing activity throughout development until adulthood.114 Injection of expression products of cloned sphingomyelinase D–encoding genes isolated from L. intermedia, L. laeta, L. reclusa, and L. boneti produces characteristic lesions in rabbits.169,299,303 Sphingomyelinase D activity has been detected from a sampling of worldwide representatives of Loxosceles.35,36 Therefore, all species in this genus are suspected to be capable of bites resulting in dermonecrosis. Many of these species live in habitats that make them unlikely to encounter humans.
Sphingomyelinase D is postulated to operate by a variety of mechanisms, including cell membrane–binding complement activation and polymorphonuclear leukocyte neutrophil (PMN) chemotaxis.105,241,274,307,308 Lesions are inhibited in rabbits by pretreatment with nitrogen mustard to deplete PMNs. Histologic studies suggest similarities between venom-induced lesions and those seen with the Arthus and Shwartzmann phenomena.274
Some vertebrate species, such as rats and fish, are essentially unaffected by Loxosceles venom; others, such as rabbits, mice, and dogs, are highly susceptible to its effects.263 Injected into humans, the venom is a hemolysin and cytotoxin, with enzymatic activities that may cause dermonecrosis and hemolysis. Pathogenesis of the human lesion is not well understood but depends on the functions of complement and PMNs.17,264 Recent works suggest that venom toxins act as proteases against constituents of plasma and basement membranes. Because of their degenerative nature, these proteases may be a plausible mechanism for the hemorrhage, delayed wound healing, renal failure, and associated spreading of other toxins seen in Loxosceles envenomations.307
Venom from L. reclusa has a direct hemolytic effect on human erythrocytes; this process depends on the presence of serum components that include C-reactive protein and calcium.145,303 Platelet aggregation also is calcium dependent and is induced in vitro with sphingomyelinase D; this process may activate the prostaglandin cascade. Platelet aggregation appears to depend on serum amyloid protein, a serum glycoprotein of previously unknown significance.104,244,262 Lysis of erythrocytes has been shown to be induced by Loxosceles sphingomyelinases dependent on activation of complement by the alternative pathway, caused by induction of surface glycophorin cleavage. Cleavage of glycophorins, observed after incubation of erythrocytes and Loxosceles toxins, was a result of activation of an endogenous membrane–bound metalloproteinase.298,307
Because Loxosceles venom provokes an immune response in experimental animals, efforts to develop diagnostic tests are based on antigen or antibody detection in human blood. In 1973, Berger and associates28 reported an in vitro lymphocyte transformation assay for L. reclusa venom, which turned positive in the lymphocytes of exposed individuals within 4 to 6 weeks of initial exposure. This test may help to document prior exposure but not to diagnose envenomation at the time of the initial bite. Barrett and coworkers23 reported a passive hemagglutination inhibition test using rabbit antibody and human erythrocytes incubated in vitro with venom from L. reclusa. Cardoso and associates,50 observing that efforts to detect antigen in human serum may fail because of insufficient antigenemia, have demonstrated the presence of L. gaucho venom in biopsy homogenate using enzyme-linked immunosorbent assay (ELISA). Barbaro and colleagues21 demonstrated circulating IgG against L. gaucho venom detectable between 9 and 120 days after the bite in 4 of 20 patients.
Some of the variability in clinical presentation among victims of Loxosceles envenomation may be caused by differences in the venom of males and females. Female L. intermedia spiders produce a greater amount of more potent venom than do males.69
Clinical Presentation
Necrotic arachnidism, or loxoscelism in the case of bite by spiders of the genus Loxosceles, refers to the clinical syndrome that follows envenomation by a variety of spiders, for which L. reclusa, the brown recluse spider, is the prototype. The bites of these spiders often result in serious cutaneous injuries, with subsequent necrosis and tissue loss. Less often, severe systemic reactions may occur with hemolysis, coagulopathy, renal failure, and even death.144,321
Reports of severe reaction to spider bites possibly attributable to brown spiders date back to 1872, in a report of a 45-year-old Texan woman with a febrile illness accompanying a large necrotic lesion of her thigh.54 In 1896, death from renal failure accompanying another bite in Texas was reported.232 Spider bite was reported as a cause of blackwater fever (massive hemoglobinuria) in Tennessee in 1940.117 The first documented case of loxoscelism (from L. rufescens) was reported by Schmaus267 in Kansas in 1929. L. laeta was identified as the cause of similar lesions in South America in 1937, and L. reclusa was the cause of necrotic arachnidism in the midwestern Unite States by 1958.9,10 Since then, numerous cases of cutaneous and more severe reactions have been attributed to spiders of the genus Loxosceles.
The clinical spectrum of loxoscelism ranges from mild and transient skin irritation to severe local necrosis accompanied by dramatic hematologic and renal injury. Isolated cutaneous lesions are the most common presentation, and most bites may resolve spontaneously without the need for medical intervention.27,28 Many clinicians distinguish between simple local presentation and more severe systemic, or viscerocutaneous, loxoscelism.
Local symptoms usually begin at the moment of the bite. A sharp stinging sensation is possible, although a victim may be unaware of having been bitten. Frequently, the bite site corresponds to a portal of entry or a region of constriction of clothing, such as cuff, collar, waistband, or groin area. The stinging usually subsides over 6 to 8 hours and is replaced by aching and pruritus as the lesion becomes ischemic from local vasospasm. The site then becomes edematous, with an erythematous halo surrounding an irregular violaceous center of “incipient necrosis” (actually hemorrhage and thrombosis).46,257,303 A white ring of vasospasm and ischemia may be discernible between the central lesion and the halo. Often, the erythematous margin spreads irregularly in a gravitationally influenced pattern that leaves the original center eccentrically placed near the top of the lesion (Figures 52-12 to 52-14). In more severe cases, serous or hemorrhagic bullae may arise at the center within 24 to 72 hours, and an eschar forms beneath. After 2 to 5 weeks, this eschar sloughs, leaving an ulcer of varying size and depth through skin and adipose tissue, but sparing muscle.138 Lesions involving adipose tissue may be extensive, perhaps from lipolytic action of the venom.159 The ulcer may persist for many months, leaving a deep scar.201,253,324 Local sequelae depend on the anatomic location. Persistent segmental cutaneous anesthesia has been attributed to nerve injury after a recluse bite on the side of the neck.127 Epiglottic and periepiglottic swelling severe enough to require endotracheal intubation has been reported in a recluse bite involving a child’s ear.137
FIGURE 52-12 Brown recluse spider bite after 6 hours, with central hemorrhagic vesicle and gravitational spread of venom.
(Courtesy Paul S. Auerbach, MD, and Riley Rees, MD.)
FIGURE 52-13 Brown recluse spider bite after 24 hours, with central ischemia and rapidly advancing cellulitis.
(Courtesy Paul S. Auerbach, MD.)
The bite of the somewhat larger South American spider L. laeta is reported to cause intense pain and extensive edema, with proportionately less necrosis than that caused by L. reclusa. The edema is notoriously prominent with facial bites and resolves over 2 to 4 weeks.264
Systemic involvement is less common but may occur in combination with cutaneous injury from any Loxosceles species; it occurs more frequently in children but may be seen in adults.233,300 Systemic reaction may develop in cases with minor-appearing local findings, making diagnosis difficult.303 When systemic involvement occurs, hemolytic anemia with hemoglobinuria is often the prominent feature, usually beginning within 24 hours of envenomation and resolving within 1 week.83 During this time, measured hemoglobin may drop markedly, accompanied by jaundice and hemoglobinuria. The anemia is usually Coombs’ test negative, but two cases of Coombs’ positive anemia have been reported.321 Fever, chills, maculopapular rash, weakness, leukocytosis, arthralgias, nausea, vomiting, thrombocytopenia, disseminated intravascular coagulation (DIC), hemoglobinuria, proteinuria, renal failure, and even death have been reported.32,111,210,321 McDade and co-workers190 reported on six adolescents treated for acute hemolytic anemia from presumed L. reclusa bites. The patients, all previously healthy, were treated for an acute systemic illness. Substantial anemia occurred in all six, with a median hemoglobin level of 7.1 g/dL. Direct antiglobulin test (DAT) was positive for surface complement component C3 in all, and surface immunoglobulin G (IgG) was detected in three patients. All patients developed reticulocytosis, hyperbilirubinemia, and local dermonecrosis.
A case report by de Souza and associates74 illustrates critical complications of Loxosceles envenomation resulting in skin necrosis, rhabdomyolysis, hemolysis, coagulopathy, acute kidney injury, and electrolyte disorders. A 26-year-old man in Brazil was bitten on his trunk while getting dressed. Twenty hours later, he sought treatment at a hospital and was given anti-Loxosceles antivenom and supportive care. The spider was brought with the patient and was positively identified as Loxosceles. Over several hours, the man became critically ill with abdominal pain, headache, nausea and vomiting, oliguria, and respiratory distress. Forty eight hours after the bite, he was transferred to an intensive care unit in a specialty hospital. He had generalized exanthem, jaundice, and conjunctival hyperemia. The bite site was edematous, with vesicles and ecchymosis. Renal function deteriorated, and he was begun on hemodialysis on day 2, and progressed to develop hemolysis with Hgb of 4.7 g/dL on day 7. On day 30, hemoglobin levels stabilized in the absence of transfusions, and the lesion had evolved to eschar with areas of necrosis. Hemodialysis was discontinued on day 35 when creatinine levels began to normalize. He was discharged, and follow-up on day 61 indicated a normal creatinine level.
The diagnosis of loxoscelism is based on spider observation and identification, typical history, and local and systemic signs. The differential diagnosis of the local injury includes bacterial and mycobacterial infection, herpes simplex, decubitus ulcer, burn, embolism, thrombosis, direct trauma, vasculitis, Lyme disease, and pyoderma gangrenosum.5,162,235,238,290 There is no universally accepted or available laboratory test to aid in diagnosis of Loxosceles envenomation. However, in one case, a venom-specific enzyme immunoassay was used to determine the cause of a suspicious skin lesion in a 57-year-old man. The assay was performed on both a lesional punch skin biopsy and a hair plucked from the lesion. In both samples, the presence of Loxosceles venom was detected, indicating that use of a hair from the lesion negated the need for a punch skin biopsy.
A series of five proved or suspected L. reclusa bites to women in the second and third trimesters of pregnancy has been reported. Despite significant local injuries, rash, and microhematuria, no fetal injury was noted.4
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