Brown Recluse Spider Bite: A Rare Cause of Necrotic Wounds

Author(s): 
Pamela S. Norden, MD, MBA, and Tania J. Phillips, MD, FRCPC

A 55-year-old white woman presents with a 9-month history of nonhealing ulceration inferior to the right axilla. The patient does not recall any trauma or antecedent event but remembers cleaning a garage in northern California 3 days prior to ulcer appearance. The wound was initially small but subsequently enlarged and developed satellite ulcers. Multiple courses of both topical and oral antibiotics and topical steroids did not improve the condition. The patient reports that nonadherent granulation occurs and that the ulcer often produces clear drainage, bleeds easily, and is extremely painful. She denies that the affected site was ever blue, gray, or black in color. After months of evaluation by numerous physicians, the patient is diagnosed with a brown recluse spider bite.
Physical examination is notable for a 5 cm x 4 cm well-demarcated circular ulcer of the right lateral chest, inferior to the axilla (Figure 1). The left lateral border shows overgranulation. The right lateral aspect reveals increased depth with fibrinous exudate. Three adjacent superficial ulcers, each approximately 1 cm in diameter, are also present. The surrounding skin is notable for macular erythema. There is no cervical or axillary lymphadenopathy. The remainder of the patient’s full skin examination is within normal limits. Scars are noted on bilateral breasts from prior mastectomy and reconstruction surgery.
Has the patient been correctly diagnosed?

Background

The brown recluse spider (Loxosceles reclusa) is the most common of the Loxosceles species in the United States.1 Human Loxosceles bites were first described in the literature1 in 1879 and were first associated with necrosis2 in 1958. While the majority of wounds caused by this spider do not require medical attention, bites may result in necrotic skin lesions, hemolysis, and renal failure. Each year, approximately 10,000 spider bites are reported to poison control centers in the US. In 1994, 1,835 of these were attributed to L. reclusa.3
The brown recluse spider is found in the southern central states of the midwestern region of the US (Figure 2).4 The heavy concentration of these spiders in this region is primarily attributable to its warm climate and moderate winters.5 Similar species found in southern California, Arizona, and Texas are known by common names, such as the desert recluse and the Arizona recluse. Many physicians incorrectly refer to all of these species as brown recluse spiders.4
Verified reports of spider travel outside of the native area are rare and almost always involve single spiders.4 Bites are uncommon in locations where spider populations are abundant and are distinctly rare in nonendemic regions. A collaborator in a 2001 study in Kansas collected more than 2,000 brown recluse spiders in her home, but no one in the home ever showed evidence of a bite.6
In contrast to the majority of spider species, which have 8 eyes, recluse spiders possess 3 pairs of eyes (dyads) on the anterior portion of the cephalothorax. The dorsum of the recluse cephalothorax is notable for a dark-brown violin-shaped marking (Figure 3). Though spiders may darken as they age and obscure the marking, these 2 findings often assist the layperson in identifying the recluse.7 Other distinguishing characteristics include an abdomen that lacks a coloration pattern and legs covered with fine hairs, in contrast to the thickened spines of other species.4 Brown recluse spiders often seek shelter in places away from plain view, such as abandoned buildings, basements, dresser drawers, stairwells, and clothing. The spider bites only when forced into contact with human skin.5

Clinical Presentation

Numerous attempts have been made to classify the clinical spectrum of loxoscelism, the condition of human envenomation by a Loxosceles spider. Among these are the following categories proposed by Gendron:8 1) bites in which little if any venom is injected, 2) bites characterized by a cytotoxic reaction, and 3) bites that cause systemic involvement. Other classification schemes link lesion size with the presence of systemic symptoms, which is often done in the clinical assessment of snake bite severity. The utility of such classification is questionable, because lesion size does not reliably predict the development of systemic symptoms.7
As noted in a case series of L. reclusa envenomation seen in a university dermatology clinic,9 only 16% of patients reported awareness of the initial bite, which was typically experienced as a mild pinch. A post-bite burning sensation or pain was noted as the first symptom by 53% of patients. Other symptoms that developed after the bite include localized pruritus (26%) and fever (16%). In a survey of family physicians,10 the majority of patients (56%) indicated that they were either asleep or were unsure of the circumstances at the time of the bite. The remainder of patients reported involvement in activities that are associated with a high probability of encounter with a brown recluse spider, such as working in storage areas, getting dressed, or working outdoors. The extremities were most often affected with the legs (53%) involved more often than the arms (37%). Other areas of involvement included the torso, face, and neck. All patients developed localized reactions ranging from mild erythema to severe cutaneous necrosis, which was sometimes associated with a central punctum (37%), edema (26%), or induration (21%).9 A similar study of 111 patients diagnosed in the emergency setting revealed comparable findings.11
Within 24 hours after the bite, the local area surrounding the bite site typically turns a reddish-blue color and may develop a blister. The affected area may exhibit the “red, white, and blue sign” consisting of erythema, ischemia, and thrombosis.12 There may be loss of light touch sensation in the center of the infarction. The margins, however, are painful.13 The ischemia of the central blister causes necrosis in 3–4 days with development of eschar between the fifth and seventh days.8 In addition, subcutaneous fat may liquefy, presumably due to the action of venom lipase, which leaves a depressed scar. This is more common in fatty areas, such as the thigh.9
The likelihood of necrosis in brown recluse spider bites is unclear. In one study, 45% of patients diagnosed with a brown recluse spider bite presented with a necrotic lesion. However, a necrotic skin lesion is seen in only 8% of patients who present a spider for examination and in only 22% of patients who report seeing a spider around the time of injury. Because the presence of necrosis may lead to the erroneous diagnosis of brown recluse spider bite, the true frequency of necrosis is unknown.11
In the previously referenced retrospective case series, 58% of lesions developed necrosis with a maximum size of 1.7 cm x 2.3 cm.9 Maximum lesion size typically occurred between 5 and 42 days after the bite. Total healing time ranged from 5 days to more than 17 weeks, with a mean of 5.6 weeks. The most severe lesions (those with areas of skin necrosis greater than 1 cm2, extensive erythema, ulceration, and edema) took an average of 74 days to heal. Lesions with areas of necrosis less than 1 cm2 healed within 22 days, and those without necrosis healed within 8 days. Increased lesion severity was associated with prolonged healing time.9
Systemic symptoms of loxoscelism may include fever up to 105?F, chills, nausea, vomiting, joint pain, seizures, and hematologic manifestations including thrombocytopenia, hemolysis, and disseminated intravascular coagulation.14,15 The syndrome rarely progresses to hemoglobinuria, renal failure, and death. No confirmed fatal brown recluse bites have been reported, but 8 presumptive cases are documented in the literature.12 Symptoms typically occur 24 to 48 hours after the bite, and children are more susceptible than adults.8 A generalized erythema or scarlatiniform rash has been described in about 25% of patients with systemic symptoms2,16 and is noted to be more severe in patients exposed to higher venom doses.7 Notably, the size of the lesion caused by the bite does not predict the development of systemic symptoms.12 After 72 hours, new systemic symptoms are unlikely to develop.17

Pathophysiology

Although the total venom volume delivered by a single bite is nominal (4 mL), venom has many potent components, among them alkaline phosphatase, ribonucleotide phosphohydrolase, esterase, hyaluronidase, and sphingomyelinase D.2,8,9,12 The venom may also be accompanied by spider stomach enzymes including hydrolase, protease, and lipase, which may increase cutaneous necrosis.18 Some of these factors may remain present at the bite site for up to 5 days after the initial insult.19
Hyaluronidase, also referred to as “spreading factor,” is believed to be responsible for venom spread throughout the subcutaneous tissue.20 Sphingomyelinase D is accountable for the majority of clinical findings associated with the brown recluse spider bite and has multiple effects including calcium-dependent erythrocyte lysis, complement activation, platelet aggregation, vascular endothelial cell activation, and enzymatic degradation of myelin in nerve sheaths.12 These actions are further potentiated by the binding of serum amyloid protein to the sphingomyelinase-D-altered membranes of platelets.21 C-reactive protein may play a similar role.12 In addition, serum amyloid protein may contribute to wound chronicity by inhibiting elastase, an enzyme that participates in the degradation of necrotic tissue.21 The functions of various venom components are summarized in Table 1.

Diagnosis

The brown recluse spider bite often presents a diagnostic challenge because bites from other spider species and a variety of dermatologic conditions may produce similar clinical presentations. As patients rarely present with a spider for positive identification, diagnosis is infrequently definitive. Misdiagnosing a necrotic wound as a brown recluse spider bite may result in inappropriate treatment and delay necessary care.22 Reported misdiagnoses include Lyme disease, cutaneous anthrax, and chemical burn. In most of these reports, no spider is positively identified in association with the wound, and the diagnosis is based solely on physical examination.23–25 In a retrospective review of 111 patients diagnosed with brown recluse spider bites in the emergency room setting, 12% of patients presented a spider for evaluation; 20% saw a spider around the time of the bite; and the remainder of the diagnoses were based solely on clinical findings. Of note, this study was performed in an area endemic to the brown recluse spider.11
Vetter, an expert entomologist who has published repeatedly on the overdiagnosis of brown recluse spider bites, favors a lesion classification scheme devised by Anderson to facilitate accurate diagnosis and guide appropriate treatment (Table 2).26 Experts generally agree that lesions associated with dermal necrosis that occur in areas endemic to the brown recluse spider should arouse suspicion. Surprisingly, in areas where the brown recluse spider is not endemic, physicians frequently make this diagnosis. Vetter notes that the state of Florida reported 95 loxoscelism diagnoses from 21 counties under the jurisdiction of the Tampa Poison Control Center in the year 2000. No brown recluse spiders, however, have ever been collected in these counties.27,28 Furthermore, a 1990 survey of 940 South Carolina physicians revealed 478 reports of loxoscelism. An arachnologist who works extensively in South Carolina, however, has never collected a Loxosceles spider nor had one submitted to him for identification in the state.28
In addition, Vetter has examined multiple specimens throughout the United States. He concludes that many nonarachnologists misidentify spiders, which further contributes to diagnostic difficulty.26
A number of diagnostic tests are currently in development. A study on guinea pigs29 revealed a passive hemagluttination test to be 90% sensitive and 100% specific up to 3 days after envenomation. The test reliably distinguished brown recluse spider venom from the venom of 4 unrelated spider species. Samples were obtained from skin lesion exudate. In addition, researchers at the University of Michigan30 published a human case report of a rapid, competitive, venom-specific enzyme immunoassay that is capable of detecting Loxosceles venom in lesional hair shafts up to 4 days after the initial insult. An increase in the concentration of IL-8 was noted in the patient’s dermal biopsy, making this cytokine a potential marker for brown recluse spider bites. A polyclonal antibody-based Loxosceles species enzyme-linked immunosorbent assay was also developed by the University of Michigan and is capable of detecting less than 0.1 ng of venom. Cross-reaction with 2 arachnid species was noted, and in-vivo testing has yet to be performed.31 Despite these advances, a reliable laboratory test approved for use in the clinical setting does not exist.

Treatment

The appropriate treatment after a bite remains controversial and is dictated by the extent and severity of involvement. For mild bites, consensus dictates that initial treatment should include thorough cleansing of the wound site, administration of analgesics, a tetanus vaccine if indicated,7 and aspirin to counteract platelet aggregation. Therapy consisting of rest, ice compresses, and elevation (RICE) is also encouraged to minimize inflammation and venom spread.32 The application of heat is contraindicated, as it may induce blisters, necrosis, or ulceration.32 If ulceration is present, antibiotics should be added for infection prophylaxis.32 While antibiotics are not always indicated, the majority of patients (approximately 86% in one study) are treated presumptively.11 All authors who have written on the subject concur that patients should be observed closely. Systemic symptoms should prompt urgent hospitalization.
Steroids have been frequently advocated for treating brown recluse spider bites,33 although neither systemic nor intralesional steroids have been observed to alter lesion size or prevent skin necrosis.34,35 Furthermore, steroids could be contraindicated if the etiology of the lesion is an entity other than the brown recluse spider bite. Steroids, however, do have a clearer role in treatment for systemic symptoms, as they may protect kidney function and decrease hemolysis, especially in children.36
Though dapsone is frequently prescribed, controlled clinical trials on humans have never been performed, and animal studies have yielded variable results. Several reports have shown a decrease in the average size of necrotic lesions in animals treated with dapsone.12,37 Other studies have been unable to demonstrate clinical benefit in this condition.38 An uncontrolled human study demonstrated improved outcomes and decreased need for surgery in patients treated with dapsone.39 This medication is thought to work by inhibition of neutrophil chemotaxis and suppression of leukocyte integrin function.37 Dapsone also diminishes cutaneous damage from sphingomyelinase D by inhibiting granule secretion from neutrophils.12
Dapsone is reserved for severe cases because of its side-effect profile. Almost all patients will develop dose-related hemolysis, while aplastic anemia, agranulocytosis, and methemoglobinemia occur rarely. All patients should be screened for glucose-6-phosphate dehydrogenase deficiency prior to starting therapy. Other associated adverse effects include peripheral neuropathy, cholestatic jaundice, and hypersensitivity reactions.8,37 These side effects may be similar to the systemic findings associated with brown spider envenomation, further distorting the clinical picture. Dapsone should be started at 50 mg by mouth daily with an increase to 100 mg daily if needed.12
Surgical excision, another potential treatment, plays a limited role in brown recluse spider bite lesions. Excision is advisable only if the lesion is large and has stabilized in size.7,40 A prospective study compared patients treated with immediate surgical excision to those treated with dapsone followed by delayed surgical excision. Early surgical intervention delayed wound healing and in certain cases caused significant scarring, both by increasing inflammation and by accentuating the effects of venom. A small subset of patients may develop nonhealing ulcers similar in appearance to pyoderma gangrenosum after a spider bite lesion is excised.39 In these cases, gentle eschar removal of stable lesions may be appropriate.12
Hyperbaric oxygen has been hypothesized to decrease wound damage by limiting the toxicity of sphingomyelinase D. This treatment is also thought to promote wound healing by increasing fibroblast collagen production. Studies have failed to demonstrate a definitive benefit.7,38
Other options include nitroglycerin patches and electric shock guns, though experience with these treatment modalities is primarily anecdotal.41,42 While antivenin in combination with dapsone has proven benefit in animals, it is not available commercially at this time and must be administered within the first 24 hours.7

Conclusion

The patient described in the introduction to this article is unlikely to have experienced a brown recluse spider bite. Though she reports cleaning a basement prior to lesion appearance, the basement was not located in an area endemic to the brown recluse spider. She also denies seeing a spider around the time of injury. The patient did not experience a pinch or burning sensation prior to the appearance of ulceration, nor was there any color change suggestive of a necrotic wound.
The brown recluse spider bite may present with mild erythema and local necrosis or with systemic involvement including hemolysis, disseminated intravascular coagulation, and renal failure. In clinical practice, loxoscelism may be difficult to diagnose, as patients rarely provide a spider for positive identification. Historical details and descriptions of lesion appearance are not always reliable. An accurate laboratory test approved for use in the clinical setting would be extremely helpful but does not exist at this time. To further complicate the subject, opinions among experts differ greatly regarding the classification of clinical lesions, the controversial available treatments, and the extent to which overdiagnosis occurs.
Physicians must be aware that because brown recluse spider bites occur infrequently in endemic areas, loxoscelism should be considered a diagnosis of exclusion in nonendemic regions. Nonetheless, it is critical for physicians to recognize the early stages of loxoscelism; if the diagnosis is missed, the patient may be at risk for life-threatening complications.

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