Worldwide, almost 4,000 genera comprise more than 40,000 known species of spiders; only two are of clinical importance in the United States.(1) The "brown spiders," most commonly represented by the brown recluse from the genus Loxosceles, are responsible for many cases of spider envenomation in the southern United States. The "widow spiders," represented by the genus Latrodectus, are the other spiders of clinical significance. The common black widow and the less common brown widow are found in North America and around the globe.

Death from spider envenomation in the United States is rare. Only a few fatal cases have been reported in the past 100 years, making spider envenomation far less common than death from other insect stings, which cause death primarily from anaphylactic reactions. Because every physician in the United States is likely to encounter a patient envenomated by one of these spiders at some point in his or her career, a working knowledge of the presentation and clinical management of people bitten by spiders is important.

Brown Recluse Spiders

Identification

Brown recluse spiders, Loxosceles reclusa (Figure 1), are usually about 2 to 3 cm in length (about the size of a thumbnail) but they can grow larger. They are found from coast-to-coast in the United States but predominantly in the southern states.(2) Other species of Loxosceles are noted elsewhere in the world.

Brown recluse spiders are typically light brown but they can vary from light to dark or even black. They usually have characteristic markings on the dorsal side of their cephalothorax, with a line coming from it in the shape of a violin. This marking is the basis of its nickname "fiddleback spider" or "violin spider." "Recluse" derives from the normal habitat for these spiders — attics, woodpiles, barns, and other remote areas where human traffic is not common. They are most active during the evening hours from spring to fall.

In the typical clinical presentation following a bite, the identity of the spider is rarely confirmed. There are several reasons for this: (1) many other conditions mimic the presentation of a brown recluse bite, (2) the offending spider is usually not seen and (3) there is no commercially available assay to detect spider venom in blood or tissue.(3)

Pathophysiology

Envenomation by the brown recluse spider can cause significant cutaneous injury, with tissue loss and necrosis. This local tissue effect has been termed dermonecrotic arachnidism. At least five species of Loxosceles spiders have been associated with this clinical picture but L. reclusa is most commonly responsible. In rare cases, a more severe reaction (systemic loxoscelism) develops, which includes hemolysis, coagulopathy, renal failure and occasionally death. Systemic involvement appears to be more common in children but can affect people of any age.(4)

Venom of the brown recluse, like that of many other brown spiders, is cytotoxic and hemolytic. It contains multiple components, including enzymes such as hyaluronidase, deoxyribonuclease, ribonuclease, alkaline phosphatase and lipase. Sphingomyelinase D is the protein component thought to be responsible for the tissue destruction and hemolysis caused by brown recluse spider envenomation.(5) The venom elicits an intense inflammatory response in the skin, which is mediated by arachidonic acid, prostaglandins and chemotactic infiltration of neutrophils. This process is amplified by an intrinsic vascular cascade involving C-reactive protein and complement activation. These and other factors contribute to the local and systemic reactions of necrotic arachnidism.

Clinical Presentation

The bite of the brown recluse spider produces minimal sensation initially and often goes unnoticed by the victim until several hours later, when the pain intensifies. As the venom causes local vasospasm and tissue ischemia, the mild stinging sensation is replaced over 6 to 8 hours by severe pain and itching. Typically, a single clear or hemorrhagic vesicle develops at the bite site within 24 to 72 hours. This vesicle later ruptures and forms a dark eschar, where tissue necrosis begins. The combination of ischemia and local tissue edema contribute to the appearance of an erythematous halo around the lesion. As the venom spreads into the surrounding tissues, the erythematous margin continues to enlarge, usually in a circular fashion. The extent of local tissue involvement is determined by multiple factors, including the amount of venom injected, the location of the bite and the preexisting health condition of the victim. Local lesions vary from small and relatively minor to extensive and life-threatening, requiring multiple debridement procedures and skin grafting to cover the defect left by necrotic tissue.(6)(7)

The relatively recent epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) skin infections has vaulted "spider bite" as the presenting complaint in emergency departments to urban-legend proportions. Several studies have shown these skin infections to be MRSA abscesses, not spider bites (the two are similar in appearance and presentation).(8)(9)(10)

The constellation of generalized symptoms known as systemic loxoscelism occurs rarely and is not related to the extent of the local tissue reaction. Symptoms may include rash, fever, chills, nausea with vomiting, arthralgia, leukocytosis, hemolysis, disseminated intravascular coagulation (DIC), renal failure, coma and death.(11)

Treatment

Pre-hospital

At the time of the initial bite, application of a cool compress may lessen the severity and rapidity of the venom activity. Only trained healthcare providers should undertake other measures.

Emergency Department

The treatment of brown recluse envenomation is guided by injury severity. Tetanus prophylaxis and basic wound management, consisting of local debridement, elevation and loose immobilization of the affected area, are appropriate first steps.

Because the activity of sphingomyelinase D is temperature dependent, application of a local cool compress may prove helpful and should be continued until progression of the necrotic process appears to have stopped. Caution is urged to avoid tissue damage from aggressive cooling of the skin. Conversely, the application of heat to the local wound should be avoided.(12)

In the past, diamino-diphenyl sulfone (Dapsone), a drug prescribed for leprosy and known for its leukocyte-inhibiting properties, was recommended for treatment of local lesions. However, the potential for adverse effects associated with Dapsone, especially in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, should warrant caution.(13) To date, no well-controlled studies have shown Dapsone to affect the clinical outcome of human brown recluse envenomations; therefore, its routine use cannot be recommended. If treatment with Dapsone is being considered, the patient’s G-6-PD level should be measured before treatment.(14)

Other treatments such as colchicine, steroids, nitroglycerin patches and surgical excision have been reported but insufficient data exist to support their clinical use today.(15) Some evidence indicates that hyperbaric oxygen therapy was beneficial in an animal model for reducing skin lesion size but controlled human studies of this technique have not been performed.(16) Patients exhibiting signs of systemic toxicity should be admitted and evaluated for evidence of coagulopathy, hemolysis, hemoglobinuria, renal failure and progression of the systemic illness. A simple urinalysis can provide early evidence of systemic involvement (e.g., hemoglobinuria, myoglobinuria) and can be performed easily at the bedside. Wound cultures and Gram stain may provide valuable information for treatment of local wounds.

Although no tests for brown recluse venom in tissue or blood are, at present, commercially available, several groups are developing laboratory methods of detecting the venom or venom components in tissue around the site of the bite.(17)(18) Once this technology becomes readily available, this envenomation can be studied in a randomized fashion.

Local debridement of necrotic lesions, as a conservative measure, should be performed once the wound margins have been defined. Wide excision is usually not necessary and is seldom indicated. Consultation with a plastic surgeon or other specialist with wound management experience should be sought for patients who might require delayed skin grafting or have a prolonged recovery period.

Brown and Black Widow Spiders

Identification

Five species of widow spiders are found in the United States, including L. mactans (black widow) (Figure 2) and L. geometricus (brown widow) (Figure 3). Black widow spiders live in every state. The brown widow, first reported in Florida in the early 1900s, is now detectable in all states bordering the Gulf of Mexico.(19) Female widow spiders are larger than males. The bite of a female may be clinically significant but the male’s bite is considered harmless. Brown widow envenomations are considered of little clinical importance, even though severe reactions to them have been reported.(20)

L. mactans is commonly black, measuring 1.0 to 1.5 cm in length and 2.5 to 5.0 cm overall, including its legs. These spiders have a bulbous abdomen with a characteristic red hourglass marking on the ventral surface. L. geometricus is typically light to medium brown and is comparable in size to the black widow. The hourglass marking on the brown widow is yellow or orange. Widow spiders are not aggressive; they tend to bite when they are pinned against a person’s skin. Brown widow spiders are likely to withdraw and, if threatened, will fall to the ground motionless.(19)

The webs of widow spiders are random and chaotic with no discernable pattern or shape. The nests of these spiders are typically built near the ground in dark undisturbed places such as woodpiles, crawl spaces, shrubs, flowerpots, outdoor furniture and storage areas. Many bites are sustained outdoors but widow spiders can be found inside buildings. Bites are more common in warmer months, when encounters with nesting areas are more frequent. In most cases, the offending spider is not seen by the victim. No laboratory assay is available to confirm the presence of Latrodectus venom but a marked response to antivenom administration supports the diagnosis.

Pathophysiology

On a volume-to-volume basis, black widow spider venom is considered more potent than pit-viper venom.(21) The venom of all Latrodectus species contains latrotoxins, a group of high-molecular-weight toxins that function in a similar fashion. α-Latrotoxin is a vertebrate toxin, responsible for envenomation in humans. There are also several insect-specific latroinsectotoxins and a crustacean-specific toxin α-latrocrustotoxin.(22) Latrotoxins cause massive release of neurotransmitters from nerves, deplete synaptic vesicles and prevent re-uptake. α-Latrotoxin binds to calcium-dependent receptors on presynaptic nerve terminals, resulting in exocytosis and release of γ-aminobutyric acid (GABA), dopamine, norepinephrine, acetylcholine, glutamate and neuropeptides.

Clinical Presentation

Latrodectism is the term used to describe the envenomation syndrome that results from the bite of a widow spider. The clinical picture of this syndrome is similar worldwide for all spiders in this species.

The sensation that occurs after a bite has been described as a pinprick or bee sting. The site often is unremarkable, with very few skin manifestations. In some cases, the symptoms do not progress; in others, severe effects emerge during the first hour following the bite. Pain is the most prominent symptom, often occurring at the bite site, radiating in the affected limb, and accompanied by rigidity in the back, abdomen and chest.(23) Abdominal pain may be so severe that it mimics a surgical abdomen. Muscle cramping often accompanies the pain associated with Latrodectus bites and progresses within a few hours. Local erythema may be noted with a maculopapular rash that is not confined to the bite area.(24) Some people experience diaphoresis, which may be limited to the area of the bite, but may also involve other sites, including the face and forehead.(25) Nausea and vomiting, along with headache and dyspnea, are common.(26)

Many bite victims have normal vital signs but others experience hypertension and tachycardia.(27) Additionally, clinical findings that include facial flushing, sweating, painful contortions, blepharitis, chelitis and masseter trismus, known as "facies latrodectismica," have been described. The victim may experience a feeling of impending doom (pavor mortis).(24) Symptoms usually emerge within the first hour following a bite, and progress and peak within 24 hours. Recurrent muscle pain and weakness persisting for weeks or months have been reported.

Treatment

Pre-hospital

Immediately after the bite, application of a cool compress may lessen the severity of pain if it is present. Other treatment measures should be undertaken by trained healthcare providers.

Emergency Department

Lactrodectism is rarely life-threatening. If a widow spider bite is suspected, but not confirmed, observation is indicated to monitor the patient for progression of symptoms. A tetanus booster should be administered after any spider bite.

At one time, calcium, because of its supposed mechanism of stabilizing neuronal endplates and thus preventing neurotransmitter release, was administered in an attempt to alleviate the muscle cramping and pain associated with widow bites. However, calcium has been shown to be ineffective for pain relief compared with antivenom.(25) Methacarbamol, a centrally acting muscle relaxant used in the past, also has been shown to be ineffective in relieving the effects of widow bite.(28)

Administration of opioid or other analgesics may help control the signs and symptoms associated with minor envenomations. Opioids may also be a useful temporizing measure before antivenom is administered.

Antivenom is the most effective therapy for severe latrodectism. A retrospective study showed that patients given antivenom had resolution of symptoms from 0 to 120 minutes after the end of the infusion and a shorter duration of hospital stay compared with patients who did not receive antivenom.(25) Antivenom should be strongly considered in patients exhibiting severe symptoms or systemic latrodectism. A delay in antivenom therapy may result in prolongation of symptoms from hours to days. An antivenom is available for widow spider envenomations and is very effective at alleviating the most painful effects.

Future of Antivenom Therapy

No Loxosceles (brown recluse) antivenom has been approved for use in the United States but researchers in other countries are developing forms of this product.(29) It is only a matter of time before suitable antivenom will be available in the United States. Because of the many mimickers of brown recluse bites in the United States, administration of brown recluse antivenom must be preceded by an assay that can detect venom components in tissue or blood. Only after we have an assay to ensure that venom is present will the benefits of treatment outweigh potential harm.

Several of these assays have been developed but none has been approved for use in the United States. At present, only one spider antivenom approved by the U.S. Food and Drug Administration is available in the United States. Antivenin, black widow spider, produced by Merck & Co., Inc., is a horse-derived product. While this antivenom has been the standard for years, Merck is no longer supporting its production and a national shortage alert has been issued. But, thankfully, a new black widow antivenom (Analatro^®, manufactured by Instituto Bioclon in Mexico) is undergoing phase 3 clinical trials in the United States. It consists of F(ab)² fragments that should induce fewer acute allergic and serum sickness reactions than the older product.

Conclusion

While spiders are plentiful around the globe, there are very few of clinical significance in the United States. The most important of these are the Loxosceles species (brown recluse spiders) and the Latrodectus species (widow spiders). The clinical presentations of bites from the different species vary and may be mistaken for other clinical entities. It is important for the practicing clinician to understand the scope of physical findings that may be present and to be prepared to manage the consequences of the spider envenomations.

Acknowledgment

The manuscript was copyedited by Linda J. Kesselring, M.S., E.L.S., the technical editor/writer in the Department of Emergency Medicine at the University of Maryland School of Medicine in Baltimore.