Brown recluse spiders: a review to help guide physicians in nonendemic areas. (Review Article).

Abstract: The brown recluse spider (Loxosceles reclusa) exists in significant populations mainly in the midwestern United States. Although bites can cause significant harm, envenomation is infrequent, and cases are usually clinically insignificant. Proper knowledge of the spider's habitat and lifestyle as well as the signs and symptoms of loxoscelism are needed to assess clinical cases adequately. Loxoscelism can masquerade as many serious pathologies, and vice versa, so it is important for the clinician to explore all possibilities in the differential diagnosis thoroughly. Treatments are controversial, and no conclusive test for envenomation is currently available. This review provides information to help physicians, especially in nonendemic areas, include or exclude brown recluse bite in the clinical diagnosis and provide proper care.

Key Words: brown recluse spider, Loxosceles reclusa, loxoscelism, spider envenomation

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Key Points

* Proper knowledge of the lifestyle and habitat of the brown recluse spider can provide important knowledge in making a diagnosis.

* The clinical presentation can include a wide range of signs and symptoms, and loxoscelism can masquerade as a myriad of other conditions.

* The majority of bites heal without major complications.

* Major treatment options are controversial, are reserved for only moderate to severe cases, and should be instituted only if the physician has a thorough knowledge of the possible complications.

The poisonous spider Loxosceles reclusa, more commonly known as the brown recluse spider, is the most dangerous and most prevalent Loxosceles species in the United States. (1) The majority of wounds caused by the spider's bite do not require medical attention, but bites can cause a series of problems, most notably necrotic skin lesions. Unfortunately, the line between fact and fiction regarding the brown recluse spider seems to be rather hazy as applied to geographic distribution, identification, diagnosis, and treatment. Some authors think that the diagnosis of brown recluse spider bite is made too liberally in areas where populations are scarce at best. The sources of dermonecrotic lesions are extensive, and morbidity can be high if certain diseases are mistreated. (2) In addition, treatment for severe brown recluse spider bites is still controversial, and medications have not been studied well and can have problematic side effects.(1) The right amount of knowledge about the spider and the wounds it causes, however, can help the physician to diagnose correctly the often perplexing and complicated cases that brown recluse bites, or its mimics, can present.

Proper Identification

Many publications state that the most distinctive feature of a recluse spider is a violin- or fiddle-shaped brown marking on the dorsal surface, but several species of tan, gray, or brown spiders have similar markings that can confuse an inexperienced identifier. Furthermore, the fiddle-shaped mark is consistent only in the brown recluse and the Texan recluse spiders and is often distorted and/or faded, depending on the age and condition of the specimen. (3,4) Vetter (3) stated that the diagnostic feature of a recluse spider is the unique way in which the eyes are patterned. Most spiders have eight eyes arranged in two rows of four, but the recluse spiders have six eyes arranged in three pairs, called dyads, with one pair located toward the front of the cephalothorax and the remaining two pair located farther back on either side. Other characteristics include an abdomen that is covered with fine hairs, is colored from tan to light brown, and never has a coloration pattern. The legs are covered with fine hair s as well, in contrast to the stout spines that cover the legs of nonrecluse spiders. (3) Proper identification of the spider can help to eliminate some of the confusion that surrounds diagnosis of brown recluse spider bites. Vetter (3) stated that while many species of spiders share commonalities with recluse spiders, none have the same aforementioned collection of distinctive features that are possessed by all recluse spiders.

Diagnostic Problems

Vetter has written extensively about the problem of misdiagnosis and overdiagnosis of brown recluse spider bites in California. It seems that much of the problem could be avoided if both the physician and bite victims were more educated regarding the spider's geographic distribution, markings, and lifestyle characteristics. The common name brown recluse spider refers to one species of spider that is indigenous only to an area that spans eastward roughly from southeastern Nebraska and the eastern half of Texas to the western part of Georgia. The northernmost boundary runs through southern Missouri, Illinois, and Indiana, and terminates in southwestern Ohio, and the southern extent is the Gulf of Mexico; however, brown recluse spider populations do not exist deep into Florida. (5,6) The importance of this fact alone becomes clear when one reads that a 1990 survey of South Carolina physicians reported 478 brown recluse spider bites and that in 2000, 95 of more than 300 spider bites reported in Florida occurred i n counties outside the city of Tampa, where no brown recluse spider sighting has ever been confirmed. (7) In a 2001 study, Vetter was contacted to comment on 120 brown recluse spider bite diagnoses made during a 21-month period in California, Oregon, Washington state, and Colorado, which together had verified only 21 brown recluse spiders. In contrast to these numbers, Vetter (7) reported that a collaborator in a 2001 study in Kansas had collected more than 1,500 brown recluse spiders in her house, yet no one in her family had ever shown evidence of a bite.

A serious discrepancy exists between the aforementioned reported numbers and Vetter's contention that overdiagnosis in areas where the spider is not native occurs frequently. South Carolina lists the brown recluse spider as one of two poisonous spiders present in the state, but confirmations have not been numerous. The literature states that the species was first confirmed in Goose Creek, SC, in 1976 and that "since that time, spiders have been seen in Liberty, SC (14 in one house), on the Clemson University campus, and other areas of the state." (4) Even though these confirmations are far from numerous, I do not think that almost 500 physician diagnoses in the state were wrong. Also, information substantiating or explaining the published geographic boundaries of the spider's habitat was not determined. However, some information leads me to think that misdiagnoses occur frequently.

Living Habits

Common knowledge of a spider described as "reclusive" may lead one to think that the information concerning confirmed specimens and native habitat is questionable because of the species' "secretive" nature. This is not the case, however, because the species' living characteristics and habitat contain a great deal of information that can be useful in making a recluse spider bite diagnosis. First, with regard to the question of how the spider may be moved from its native habitat, many spiders can disperse by migration or even be carried by small air currents, but the brown recluse spider must rely on the intervention of humans if it is to expand outside its range. (3,8) The recluse spider is often referred to as a house spider, because they thrive in human-altered environments such as attics, basements, and boxes and therefore are often transported when people move or in the normal flow of daily activity. Thus, it is likely that a few individuals or a small population of spiders could be transported and found i n a new location, but one should not conclude that this new population is a sign of infestation. (3,8) The brown recluse spider is reclusive because it lives in boxes, basements, and under rocks and not because it lives alone. These spiders are unusual because they are highly tolerant of conspecifics in close quarters, and decent populations are needed to render the probability of a bite significant. (7) Because bites are infrequent in areas where spider populations are high, the take-home message is that physicians who live in nonendemic areas need to be stingy when diagnosing brown recluse spider bites. It is possible for bites to occur, because translocation usually involves human belongings and contact, but the probability of a lone spider biting a human in a nonnative area is unlikely. (7,8)

Anderson (8) wrote that the minimum criteria for a verified, publishable account of a brown recluse spider bite should occur only if a spider is found and properly identified in the area where the bite took place. He thinks that if this type of confidence is not obtained, then the physician should definitely presume other causes and not loxoscelism. Because the majority of brown recluse spider bites are clinically unremarkable, one can logically conclude that many misdiagnoses are uncorrected; if the patient does not have loxoscelism or a necrotic wound that responds to similar treatment, the consequences of a mistaken diagnosis can be severe. (2,8,9) Unfortunately, the circumstances that Anderson (8) described rarely occur in the clinical setting. Therefore, a physician practicing outside the brown recluse spider's native habitat must use all available clinical information when a patient presents with a proposed brown recluse spider bite so that a mistake in treatment is avoided.

Clinical Presentation

Loxoscelism and latrodectism (caused by the black widow spider) are the only two clinically significant spider bite diseases that need a physician's treatment, and the vast majority of brown recluse spider bites are clinically insignificant and heal with minimal treatment. (1,8,9) Initial bites, if felt, are described as a mild pinch and often occur when the victim is dressing. Within the first 6 hours after the bite, pruritus, pain, and erythema can develop, followed within the first 24 hours by the formation an irregular erythematous ring around the site of the bite. (10) Under more severe circumstances, necrosis occurs within 48 to 72 hours after the bite. Initially, the site turns reddish-blue in color, significant pain is likely to occur, and the lesion evolves into an eschar. Key signs of necrosis that occur early in the progression include bullae formation, cyanosis, and hyperesthesia. It is also important to note that areas containing a large amount of adipose tissue are at increased risk for necrosis . (10) Systemic complications may accompany advanced cases of necrotic arachnidism but are not directly correlated with the severity of the cutaneous reaction. Occurring most frequently in young children, systemic complications include chills, fever, nausea, arthritic complaints, and blood abnormalities (rare). (10)

Rare but extremely dangerous complications of brown recluse spider envenomation include pyoderma gangrenosum, severe intravascular hemolysis, renal failure, pulmonary edema, and systemic toxicity. (11,12) Major complications occur in only a small minority of cases, however, and the need for complicated treatment and surgery is minimal. Often loxoscelism and necrotic arachnidism cases are grouped by severity similarly to snakebites to help guide treatment, but the usefulness of this classification scheme is questionable because little correlation exists between the development of skin necrosis and systemic symptoms. (10,11)

The above description is not a complete account of all characteristics that can accompany a brown recluse spider bite, and it seems that a patient's disease process could contain almost any constellation of symptoms. The good news remains that most people do not have severe reactions to the bite. A study in which the researchers examined the clinical presentations and outcomes of ill brown recluse spider bite patients in Nashville, TN, found that only 14% of patients had systemic problems, 9% were treated with dapsone, only 5% were admitted to the hospital, and 3% required skin grafting. (13) This information is even more impressive when one considers that the study was conducted by the major referral center in the area, which most likely saw the worst cases in the region.

Differential Diagnosis

In patients in whom brown recluse spider bite has been misdiagnosed, what was the cause? One of the main problems is that the presence of a spider is rarely confirmed, and physicians too frequently diagnose a spider bite as the cause of dermonecrotic lesions. (2,8) The potential causes of dermonecrotic wounds are extensive, and several researchers think that in areas outside the spider's native habitat, the likelihood of a bite is small, so other causes should be considered. (2,14) The many causative agents include bacterial infection, fungal infection, pyoderma gangrenosum, viruses, adverse drug reactions, other arthropod bites, thromboembolic phenomenon, Lyme disease, neoplasms, chemical burns, and necrotizing fasciitis. (1,2,14,15)

Obviously, making the correct initial diagnosis is crucial and requires that the physician know as much as possible about the spider. In the above two cases, the location of the incident would have been strong evidence in favor of excluding loxoscelism as the correct diagnosis. Each case is obviously uniquely difficult, but the more knowledge that is obtained from the patient and about the wound, the more likely it is for the cause to be uncovered.

Venom

Loxosceles venom contains numerous enzymes, and the function of each is not yet known. Enzymes include alkaline phosphatase, 5-ribonucleotide phosphohydrolase, esterase, hyaluronidase, and most important, sphingomyelinase D2 (SMD). (10,11,16) SMD is most active at 37[degrees]C, breaks down sphingomyelin to choline and N-acylsphingosine, and is responsible for calcium-dependent erythrocyte lysis. SMD does not work alone, however, because many substances are involved in the cutaneous and vascular damage that occurs. (11) Tissue injury, for example, does not occur in the absence of serum amyloid protein, whose role may involve binding to the SMD-altered membranes of platelets. SMD also causes in vitro EDTA-inhibitable platelet aggregation that may cause thrombosis through the release of multiple compounds. Pain may be heightened by the degradation of myelin nerve sheaths by SMD. (11) The disease pathway can lead to necrosis, because SMD activates the vascular endothelial cells. The venom attracts neutrophils, wh ich bind to endothelial cells but do not extravasate from the vasculature. The neutrophils then release their granules intravascularly, leading to thrombosis, ischemia, and necrosis. (11)

One of the main hurdles that physicians trying to diagnose a brown recluse spider bite face is that there is no laboratory test available to accurately verify the spider as the culprit. Thus, doctors must make purely clinical diagnoses, often relying on hazy patient recollections and a broad range of signs and symptoms. Research shows that the venom itself can be used to help clinicians make a fast and accurate diagnosis. Performing a specific enzyme-linked immunosorbent assay may be the key to unlocking the elusive puzzle caused by recluse spider envenomation.

Gomez et al (17) stated that brown recluse spider bites are often misdiagnosed, allowing treatable illnesses to run their course and increasing the risk of morbidity. Research has shown that the Loxosceles reclusa-specific assay that Gomez et al described accurately identified Loxosceles venom at less than 40 ng/100 [micro]1 homogenized rabbit tissue from a dermal punch biopsy. The purpose of their experiment was to determine the efficacy of the Loxosceles-specific assay when it is cross-reacted with a number of different North American arthropod venoms. The assay is polyclonal, meaning it reacts with multiple proteins; therefore, it was hypothesized that the assay may not be able to detect Loxosceles venom exclusively. The assay showed mild cross-reactivity with 8 of the 17 species used, but only at more elevated concentrations in the specimen. The authors also conceded that the assay would react with most Loxosceles venoms, even though it was based on L. reclusa, but asserted that the clinical benefit of t he assay is that it can identify accurately the presence of arthropod venom in the victim and not necessarily the specific species involved.

Krywko and Gomez (18) proposed and further explored the fact that a dermal punch biopsy would be undesirable because of the potential cosmetic harm it could cause. Experiments were conducted with rabbits injected with physiologic concentrations and retrieval was attempted with hair, wound aspirates, serum, and skin biopsy. Research showed that venom detection was possible for 7 days after inoculation in all samples except serum. The authors conceded that detection levels were lower in aspirate and hair than in the biopsy, but they stated that this finding is unimportant because the main point is that venom was detected.

Although this research provides valuable insight, it is not yet known whether these methods are applicable in humans. Whether biopsies, hair, a more specific assay, or some other medium of detection, the important point is that researchers are attempting to find a clinically useful means of Loxosceles venom detection. If this goal is achieved, the clinician "can direct therapeutic strategies toward supportive care and avoid unnecessary diagnostic testing or potentially dangerous therapies," a skill "that would be particularly useful in areas that are outside the natural habitat of Loxosceles species spiders." (17)

Treatment

As previously stated, the majority of brown recluse spider bites heal without medical treatment within a few weeks or months. (1,8) If treatment is needed, however, it should be monitored closely and appropriated in a conservative, case-specific manner. Initially, bites should be cleaned thoroughly and rest, ice, compression, and elevation (ie, "RICE") treatment should be initiated. Mild cases characterized by pruritus, erythema, and punctum should be treated by administering aspirin and antihistamines and possibly a tetanus vaccine. (1,10,11) Patients with wounds that begin to show signs of tissue breakdown should be administered prophylactic antibiotics (eg, erythromycin, cephalosporin) to prevent cellulitis. Bites that become necrotic and show signs of edema may respond to dapsone treatment, a drug that is thought to be effective if administered early in the course of the disease but may not always be advisable, because results are varied and side effects are problematic. (1)

Dapsone is thought to limit tissue destruction by the suppression of neutrophils, but its effectiveness is debated and its side effects may be severe. (1) Side effects almost always include dose-related hemolysis as well as possible sore throat, pallor, agranulocytosis, aplastic anemia, cholestatic jaundice, and methemoglobinemia. Unfortunately, some of these symptoms can be caused by brown recluse spider envenomation, so close patient supervision is critical when dapsone is administered. (1,10,13) One additional consideration is that patients considered for dapsone must be screened for glucose-6-de-hydrogenase deficiency, because in these patients, the drug's hemolytic side effects can be dangerous. (1,10) The current knowledge of dapsone and the circumstances surrounding brown recluse spider bites present the clinician with a difficult situation. Dapsone is thought to be ineffective if not administered within hours of the bite, but the side effects are so bad that it should not be administered prophylactic ally. (1,10) The drug is reserved only for moderate to severe cases, but the physician cannot initially determine the progression of a case. If dapsone is used, the physician must have thorough knowledge of the drug's side effects and reach a conclusive diagnosis in a timely manner. (11)

Systemic Loxoscelism can occur in mild or severe cases and is seen most frequently in children. Treatment for systemic problems is mainly supportive and includes vigorous hydration, serial complete cell blood counts, and urinalysis in severe cases. In addition, a systemic steroid should be administered to help prevent kidney failure and halt hemolysis. Steroids also have been thought to help prevent skin necrosis, but research does not support this hypothesis, and these drugs thus should be reserved only for patients with systemic problems. (1,10,11)

Surgical excision is another proposed treatment for brown recluse spider bite lesions. Excision is advisable only when the lesion is large, has progressed for approximately 6 to 8 weeks, and definitely has stabilized. Excising lesions early is inadvisable, because the process increases inflammation, may accentuate the effects of the venom, and lesion enlargement could still be occurring. Slow, gentle eschar removal of a stable lesion, however, may be appropriate. (1,10,11)

Proposed alternative treatments of dermonecrotic lesions include the administration of hyperbaric oxygen, topical nitroglycerin, and cyproheptadine, but research on these therapies is inconclusive, and thus their use is not recommended. (10,11,19,20) Only 10 to 15% of brown recluse spider bites lead to major problems (ie, unacceptable scarring, hospitalization, chronic lesions), so the odds are that intensive treatments and procedures will not be necessary. (11)

Conclusions

This review was meant to provide useful information and guidelines to enable physicians, especially those outside the native range of Loxosceles reclusa, to make efficient, accurate diagnoses of dermonecrotic wounds of unknown origin. Key points that should be taken from this article are that 1) brown recluse spider bites are relatively infrequent even in states and local areas where populations are high, so physicians in nonendemic areas should diagnose brown recluse spider bite only as a last resort after other avenues have been pursued thoroughly; (7,8) 2) a detailed history of where the supposed bite occurred and follow-up inspection of the area by the patient can provide crucial diagnostic information; 3) whenever a spider is found or brought into the physician's office, careful and professional identification should be performed; (3) and 4) if loxoscelism is suspected, the treatment administered should be conservative and the physician should monitor the patient's progress carefully, especially when ca ses become severe. (1)

Mistakes and misdiagnoses are unavoidable in some cases, but the circumstances involving brown recluse spider bite diagnosis can be precarious. Differences in opinion regarding the spider's habitat, the number of bites reported outside the spider's native range, the spectrum of bite outcomes that can occur, the many different problems that present in a similar manner, the opinions of many researchers, the potentially dangerous conditions that can be mistaken for brown recluse spider bites, the controversial treatments, and that the majority of outcomes in patients with brown recluse spider bites are good are variables that the physician must consider in a 15-minute consultation with the patient. Physicians must prevent significant harm to patients with brown recluse spider bites by acquiring the knowledge necessary to handle the minority of cases whose outcome can be devastating.

Accepted February 3, 2003.

Acknowledgment

I wrote this article under the tutelage of Dr. William Simpson, Department of Family Medicine, Medical University of South Carolina, Charleston, SC.

References

(1.) Stibich AS, Schwartz RA. Brown recluse spider bite. e Med J 2001;2: July 27.

(2.) Vetter RS, Bush SP. The diagnosis of brown recluse spider bite is overused for dermonecrotic wounds of uncertain etiology. Ann Emerg Med 2002:39:544-546 (editorial).

(3.) Vetter RS; University of California Statewide Integrated Pest Management Program (UCIPM). UC Pest Management Guidelines: Brown recluse and other recluse spiders--Home and landscape (UC ANR Publication 7468). Davis, CA, Statewide IPM Program. Available at: http://www.ipm.ucdavis.edu/PMG/PESTNOTES/pn7468.html. Accessed March 14, 2003.

(4.) Culin JD, Horton PM. Entomology Insect Information Series: Poisonous Spiders of South Carolina. Clemson, SC, Department of Entomology, Clemson University. Available at: http://entweb.clemson.edu/cuentres/eiis/medvet/MV6.pdf. Accessed March 14, 2003.

(5.) Vetter RS. Identifying and misidentifying the brown recluse spider. Dermatol Online J 1999 Nov;5(2):7. Available at: http://dermatology.cdlib.org/DOJvol5num2/special/recluse.html. Accessed March 14, 2003.

(6.) Mock DE. Home and horticultural pests: Brown recluse spiders (Pub. No. MF1158). Manhattan, KS, Kansas State University Agricultural Experiment Station and Cooperative Extension Service, July 1994, Available at: http://www.oznet.ksu.edu/library/ENTML2/MF1158.PDF. Accessed March 14, 2003.

(7.) Vetter RS. Insect information: Causes of necrotic wounds other than brown recluse spider bites. Riverside, CA, Department of Entomology, University of California-Riverside. Available at: http://spiders.ucr.edu/necrotic.html. Accessed March 14, 2003.

(8.) Anderson PC. Spider bites in the United States. Dermatol Clin 1997; 15:307-311.

(9.) Cacy J, Mold JW. The clinical characteristics of brown recluse spider bites treated by family physicians: An OKPRN Study--Oklahoma Physicians Research Network. J Fam Pract 1999;48:536-542.

(10.) Forks TP. Brown recluse spider bites. J Am Board Fam Pract 2000;13:415-423.

(11.) Sams HH, Dunnick CA, Smith ML, King LE Jr. Necrotic arachnidism. J Am Acad Dermatol 2001;44:561-576.

(12.) Williams ST, Khare VK, Johnston GA, Blackall DP. Severe intravascular hemolysis associated with brown recluse spider envenomation: A report of two cases and review of the literature. Am J Clin Pathol 1995;104:463-467.

(13.) Wright SW, Wrenn KD, Murray L, Seger D. Clinical presentation and outcome of brown recluse spider bite. Ann Emerg Med 1997;30:28-32.

(14.) Osterhoudt KC, Zaoutis T, Zorc JJ. Lyme disease masquerading as brown recluse spider bite. Ann Emerg Med 2002;39:558-561.

(15.) Vetter RS, Bush SP. Chemical bum misdiagnosed as brown recluse spider bite. Am J Emerg Med 2002;20:68-69 (letter).

(16.) Sams HH, Hearth SB, Long LL, Wilson DC, Sanders DH, King LE Jr. Nineteen documented cases of Loxosceles recluse envenomation. J Am Acad Dermatol 2001;44:603-608.

(17.) Gomez HF, Krywko DM, Stoecker WV. A new assay for the detection of Loxosceles species (brown recluse) spider venom. Ann Emerg Med 2002;39:469-474.

(18.) Krywko DM, Gomez HF. Detection of Loxosceles species venom in dermal lesions: A comparison of 4 venom recovery methods. Ann Emerg Med 2002;39:475-480.

(19.) Lowry BP, Bradfield JF, Carroll RG, Brewer K, Meggs WJ. A controlled trial of topical nitroglycerin in a New Zealand white rabbit model of brown recluse spider envenomation. Ann Emerg Med 2001;37:161-165.

(20.) Phillips S, Kohn M, Baker D, Vander Leest R, Gomez H, McKinney P, et al. Therapy of brown spider envenomation: A controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine. Ann Emerg Med 1995;25:363-368.

RELATED ARTICLE: Case Reports

A healthy 9-year-old boy from Philadelphia presented over the course of several days with a wound characteristic of a necrotic recluse bite. The boy came to the emergency department on the fourth day of his illness, and on the basis of the father's story that he "chased a brown recluse out of his kitchen" and the presence of a necrotic lesion, an incorrect diagnosis of probable arthropod bite was made. When the boy returned in worsened condition 8 days later, further evaluation revealed Lyme disease to be the correct diagnosis. (14)

Another case involved a 7-month-old in the state of New York who was initially diagnosed with brown recluse spider bite that turned out to be cutaneous anthrax. This case involved a notably difficult diagnosis, but the fact that no populations of brown recluse spiders are known to exist in the state should have made it a diagnosis of last resort. (15)

From the Occupational and Environmental Medicine Program, Medical University of South Carolina, Charleston, SC.

Reprint requests to Preston Wendell, BS, c/o Dr. William Simpson, Occupational and Environmental Medicine Program, Medical University of South Carolina, 19 Hagood Avenue, Suite 305 HOT, P.O. Box 250805, Charleston, SC 29425. Email: [e-mail]

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