Redback Spider Envenomation

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Background

The redback spider (Latrodectus hasselti) belongs to the family Theridiidae, the comb-footed spiders. Its genus Latrodectus also includes black widows, whose name may be more familiar to North American readers. The redback spider can be found throughout Australia, although it is more commonly seen in the temperate regions than in the colder, southern areas. The spider exists in higher numbers in Australia's urban and suburban areas and is virtually absent in the continent's forests. Outside of Australia, similar species of Latrodectus include Karakurt in Central Asia, Malmignatte in Europe, the Koppie spider in South Africa, and the Night Stinger in New Zealand.

The redback spider bite is the most common envenomation treated with antivenom in Australia. The female redback spider is responsible for most envenomations. She is usually 10 mm in length and has a small cephalothorax and a large, globular abdomen that bears a red, orange, or brown stripe. The male redback spider is considerably smaller than the female and is only occasionally able to cause mild envenomation.[1, 2] See the images below.



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Female redback spider showing a distinctive red stripe over the abdomen. Image courtesy of John Paterson.



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Female redback spider with egg sacs. Image courtesy of John Paterson.

See Venomous Spider Bites: Keys to Diagnosis and Treatment, a Critical Images slideshow, for help identifying and treating various envenomations.

Pathophysiology

The redback spider can cause a clinical condition referred to as latrodectism following a bite. The active ingredient in the redback's venom responsible for its toxic properties in vertebrates is a 130-kd protein, alpha-latrotoxin (aLTX). aLTX is a potent neurotoxin that works in 2 ways to produce efflux of neurotoxins from presynaptic nerve cells.

In one mechanism of action, aLTX aggregates into tetramers that form pores in neuronal presynaptic cell membranes allowing calcium influx into the cytosol and resulting in exocytosis of neurotransmitters such as norepinephrine, dopamine, acetylcholine, glutamate, and GABA. The membrane pores formed by aLTX may also be large enough for a direct efflux of small intracellular compounds that are vital for cytoplasm function.

The monomeric aLTX can also act by activating latrophilin (LPH), an aLTX receptor found on the cell surface of neuronal cells, without incorporating into the cell membrane. Latrophilin is a G protein-coupled receptor that activates phospholipase C, which, in turn, increases the cytosolic concentration of IP3 leading to release of calcium from intracellular stores. This rise in cytosolic calcium increases the rate of spontaneous exocytosis of neurotransmitters and the amplitude of evoked release. Alpha-latrotoxin is a potent venom, with an LD-50 of 20-40 µg/kg of body weight in mice.[3, 4, 5]

Epidemiology

Frequency

United States

Only the black widow spider, a close relative of the redback spider, lives in the United States. These arachnids cause approximately 2500 envenomations each year.

International

The redback spider is found in Australia, New Zealand, and southern Asia. In Australia, the spider has been blamed for 250 envenomations requiring antivenom annually. Perhaps many more cases are mild or unrecognized and do not receive antivenom.

Race

All races are susceptible to redback spider envenomation if the patient lives in an endemic area inhabited by the redback spider. One article shows more severe envenomation in Aboriginal patients, but states that this is due to a significantly longer time from envenomation to presentation in ED as compared with non-Aboriginal patients.[6]

Sex

In one study of redback envenomations in Australia, 60% of victims were female. However, most sources do not demonstrate a male/female sex discrepancy.[7]

Age

Redback envenomation may occur at any age; the median age is 35 years. Envenomation may be more dangerous in babies and small children because of the difficulty in making a specific diagnosis in that group of patients in addition to the small body size bearing the same dose of injected poison as an adult would tolerate.[7]

Prognosis

Most patients with redback spider envenomation recover fully. Accurate data regarding morbidity/mortality is difficult to gather, as there is no mandatory reporting of spider bites in Australia. There appears to be greater morbidity in pediatric and elderly patients. There have been no recorded deaths caused by redback spider bites in the past several decades.[8]

Patient Education

The web site Museum Victoria contains additional information about and photographs of the redback spider.

History

In Australia, most bites occur during the warmer months between December and April. Bites to the limbs comprise approximately three quarters of cases, and bites to the distal limbs are twice as common as to the proximal limbs; 46% in distal extremity and 26% in proximal limb. In areas without indoor plumbing, bites to the genitalia and buttocks are often seen.[9]

There is usually immediate pain at the site of the bite with or without erythema, which can progress over hours to involve the entire limb and draining lymph nodes in the axilla or groin. The pain may persist longer than 24 hours, with a median duration of 36 hours.

Local inflammation and swelling is more prominent in redback envenomations than in envenomations by other Latrodectus species, for which local symptoms are usually minimal.

Some patients then develop painful spasms of the large muscle groups; when involving the abdominal muscles, it may mimic an acute abdomen.[10]

Other common complaints include nausea, vomiting, abdominal pain, headache, and migratory arthralgias.[3]

Infants and toddlers may present with nonspecific symptoms such as irritability, inconsolable crying, and refusal to eat.[11]

Most cases are mild or unrecognized and do not receive antivenom.

The only way to definitively diagnose a redback spider bite is by positive identification of the spider, either by patient description of the typical red markings or if the spider or a digital photograph of the spider is brought to the provider.[7]

Physical Examination

Common physical findings in a patient with redback spider envenomation include tenderness and erythema at the bite site. Occasionally, one can see generalized or localized sweating, which may be remote from the bite site. Local piloerection may also be present.[7]

Systemic findings in redback spider envenomation, seen in approximately 35% of all bites, include fever, hypertension, and tachycardia.[7]

Spasms of large muscle groups are seen in some patients.

Neurological symptoms may include restlessness and insomnia, muscle weakness and twitching, and paralysis. The median duration of all effects is 48 hours.

Rare complications include myocarditis, rhabdomyolysis, and death.

Complications

Complications of redback spider envenomation are as follows:

Laboratory Studies

There are no specific laboratory studies available to diagnose latrodectism.

The serum creatine kinase, serum glucose, alanine transaminase, aspartate transaminase, and peripheral white blood cell count may be elevated,[12] but these findings are nonspecific and generally unhelpful.

In a female patient, a pregnancy test should be performed to differentiate the presentation from premature labor or other complications of pregnancy and to guide the medication choice for treatment of latrodectism.

Imaging Studies

Plain radiographs of the affected limb may be indicated to evaluate for subcutaneous air if a concern for necrotizing fasciitis exists.

Venous Doppler ultrasonography of the affected extremity may be indicated to evaluate for deep vein thrombosis if the diagnosis is unclear.

Other Tests

A 12-lead ECG should be obtained in patients with autonomic instability, chest pain, or if comorbidities are present.

Prehospital Care

Pressure immobilization of the bitten limb is not recommended due to the slow and non–life-threatening progression of symptoms. Pressure dressings may also exacerbate pain in the affected area.

Ice packs to the bite site may be helpful.

Analgesia should be provided in accordance with local protocols.

Do not administer antivenom in the field, owing to the risk of a severe allergic reaction.

Collection of the spider, if it is safe to do so without endangering providers, may aid its proper identification at the emergency department. Digital photography may be a safer way to aid in identification without handling a potentially venomous spider.

Emergency Department Care

The cornerstone of treatment of any redback envenomation is aggressive pain control; in severe cases, sedation may be necessary. There are no data to suggest superiority of any specific analgesic. Oral or parenteral NSAIDs, acetaminophen, or opioids are reasonable depending on the degree of pain. Benzodiazepines may be used for sedation if needed.

In patients with severe symptoms and signs of severe envenomation, redback spider antivenom is often given. A large amount of anecdotal and observational evidence[9, 12, 13] suggests antivenom is rapidly effective in reducing pain and systemic symptoms, although two randomized control trials (RCTs) do not show benefit over analgesia alone. A small RCT of 24 patients suggests that antivenom reduced pain more rapidly than analgesics alone but no difference in overall pain reduction and clinical outcome was noted.[14] A more recent RCT of 224 patients did not show any significant reduction in pain or systemic symptoms with antivenom administration, although a trend toward more rapid pain relief was noted.[15]

There is some controversy regarding these results,[16] however, as the treatment effect appears to be much smaller than previous experience, with most patients not experiencing pain relief at 4 hours. Consultation with a toxicologist is recommended if treatment with antivenom is being considered.

Intravenous calcium does not appear to be effective[17] and is not recommended.

If compartment syndrome due to redback spider envenomation is suspected, antivenom administration and direct measurement of intracompartmental pressure is recommended. Although compartment syndrome suspected to be caused by Latrodectus envenomation has been reported,[18] it is exceedingly rare. Prophylactic fasciotomy or fasciotomy based on clinical diagnosis of compartment syndrome should not be performed. If the compartment pressure is elevated, it should be rechecked after administration of antivenom before surgical intervention is considered.

Inpatient Care

Hospitalization is generally not required, after a period of observation, for patients whose symptoms have been alleviated with antivenom or are easily controlled with oral analgesics. Patients requiring large doses of opioid analgesics or who require sedation for symptomatic control should be hospitalized.[7] Hospitalization is also recommended in the following situations:

Consultations

The local poison control center should be consulted for spider identification and management of severe envenomations.

Consultation with a toxicologist is recommended in severe cases or in cases in which antivenom is being administered.

A surgeon may be consulted if compartment syndrome is suspected due to persistently elevated compartment pressures after administration of antivenom. 

Complications

Antivenom-associated complications are anaphylaxis and serum sickness.

Anaphylaxis (type I hypersensitivity reaction) is characterized by urticaria, wheezing, and circulatory collapse. The risk of allergic reaction in patients receiving redback antivenom is 0.5% and is higher in patients with prior exposure to horse serum proteins or history of reactive airway disease. Anaphylaxis is treated with epinephrine, corticosteroids, antihistamines, intravenous fluids, and ventilatory support in the usual medical fashion.

Serum sickness (type III hypersensitivity reaction) is characterized by fever, urticaria, pruritus, nephritis, and arthritis. This condition occurs in 1.4% of patients receiving antivenom and is self-limiting. Treatment is usually supportive, but severe cases may be treated with systemic steroids and occasionally plasmapheresis.

Prevention

Use of pesticides may prevent exposure to spiders in the home. In endemic areas, patients should be advised to inspect their clothes and shoes for spiders before wearing them.

Long-Term Monitoring

Patients should be given thorough instructions listing the symptoms of serum sickness (fever, pruritus, and arthropathy) and cellulitis and advised to seek medical care if such symptoms occur.[1]  Patients may need to undergo a short course of steroid treatment should serum sickness occur.

Medication Summary

Most cases of redback spider envenomation are mild and can be managed symptomatically using oral analgesics. Severe cases may need parenteral opioids and/or benzodiazepines for pain control and sedation.

Redback spider antivenom provides specific treatment in severe cases of envenomation. Indications for use of antivenom include severe headache, vomiting, abdominal pain, hypertension, arthralgia, or myalgia. Severe pain at the envenomation site is not considered an indication for antivenom administration.[1]  Increasing concerns exist about the possible ineffectiveness of the intramuscular route of administration of the redback antivenom.[19] A randomized trial showed no significant difference in relief of symptoms or patient outcome between intravenous and intramuscular administration of antivenom.[20] A more recent study did not show significant benefit even via the intravenous route; see the discussion below.

Tetanus vaccine should be given to all patients who are not already vaccinated, are due for a booster, or whose vaccination status is unknown.

Redback spider antivenom

Clinical Context:  Redback spider antivenom is produced by Commonwealth Serum Laboratories Ltd, Australia.

Class Summary

The antivenom consists of equine immunoglobulin G (IgG) fragments raised against alpha-latrotoxin (aLTX). Each ampule contains 500 units of neutralizing capacity against the Australian redback spider venom, with an average volume of 1-1.5 mL per ampule. The antivenom is typically administered by intramuscular injection, although the intravenous route has become favored. Indications for use of antivenom include severe headache, vomiting, abdominal pain, hypertension, arthralgia, or myalgia. Severe pain at the envenomation site is not considered an indication for antivenom administration.

Increasing concerns exist about the possible ineffectiveness of the intramuscular route of administration of the redback antivenom. A randomized trial showed no significant difference in relief of symptoms or patient outcome between intravenous and intramuscular administration of antivenom. A more recent study did not show significant benefit even via the intravenous route; see the discussion above.

The risk of allergic reaction to the antivenom is 0.5% and is higher in patients with a history of horse allergy or prior exposure to equine immunoglobulin. Before using the antivenom, ensure the ability to manage hypersensitivity reaction and check for availability of the appropriate resuscitation/intubation equipment. The risk of serum sickness after exposure to the antivenom is 1.4%.

Administration of antivenom requires informed consent. If feasible, a discussion of the risks, benefits, and alternatives should be held with the patient prior to administering antivenom.

Patients discharged after receiving antivenom should receive clear return instructions in the case of delayed hypersensitivity reactions.

Acetaminophen

Clinical Context:  Acetaminophen is the drug of choice for pain in patients with documented hypersensitivity to aspirin or NSAIDs or in patients with upper GI disease or who are taking oral anticoagulants. It is effective in relieving mild to moderate acute pain; however, it has no peripheral anti-inflammatory effects. Acetaminophen may be preferred in elderly patients because of fewer GI and renal adverse effects.

Ibuprofen

Clinical Context:  Ibuprofen is the drug of choice for patients with mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. The intravenous form (Caldolor) is available only for hospital use and is indicated for pain or fever.

Class Summary

Oral acetaminophen or NSAIDs are reasonable as first-line therapy or in those without severe symptoms.

Morphine (Arymo ER, Astramorph, Depodur)

Clinical Context:  Morphine sulfate is the drug of choice for analgesia because of it has reliable and predictable effects, a good safety profile, and is easy to reverse with naloxone. Various intravenous doses are used; it is commonly titrated until the desired effect is obtained.

Fentanyl (Sublimaze)

Clinical Context:  Fentanyl citrate is a synthetic opioid that is 75-200 times more potent and has a much shorter half-life than morphine sulfate. It has less hypotensive effects and is safer in patients with hyperactive airway disease than morphine because of minimal-to-no associated histamine release. By itself, it causes little cardiovascular compromise, although the addition of benzodiazepines or other sedatives may result in decreased cardiac output and blood pressure.

It is highly lipophilic and protein-bound. Prolonged exposure leads to accumulation in fat and delays the weaning process. Consider continuous infusion because of the short half-life of fentanyl. A parenteral form is the drug of choice for conscious sedation analgesia. It is ideal for analgesic action of short duration during anesthesia and for the immediate postoperative period.

Fentanyl citrate is an excellent choice for pain management and sedation with short duration (30-60 min) and is easy to titrate. Effects are easily and quickly reversed by naloxone.

After the initial parenteral dose, subsequent parenteral doses should not be titrated more frequently than every 3 hours or every 6 hours thereafter.

The transdermal form is used only for chronic pain conditions in opioid-tolerant patients. When using the transdermal dosage form, most patients are controlled with 72-hour dosing intervals; however, some patients require dosing intervals of 48 hours.

Hydromorphone

Clinical Context:  Hydromorphone is a potent semisynthetic opiate agonist similar in structure to morphine. It is approximately 7-8 times as potent as morphine on mg-to-mg basis, with a shorter or similar duration of action.

Class Summary

Those with severe envenomations may need aggressive pain control with parenteral opioids.

Lorazepam (Ativan)

Clinical Context:  Lorazepam is a sedative hypnotic in the benzodiazepine class that has a short onset of effect and relatively long half-life.

Diazepam (Valium)

Clinical Context:  Diazepam modulates the postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. Diazepam also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

It rapidly distributes to other body fat stores. Twenty minutes after the initial intravenous infusion, the serum concentration drops to 20% of C MAX . Individualize the dosage and increase cautiously to avoid adverse effects.

Midazolam (Versed)

Clinical Context:  Because midazolam is water soluble, it takes approximately 3 times longer than diazepam to peak EEG effects. Thus, the clinician must wait 2-3 minutes to fully evaluate sedative effects before initiating a procedure or repeating a dose. Midazolam has twice the affinity for benzodiazepine receptors than diazepam. It may be administered intramuscularly if vascular access cannot be obtained.

Class Summary

Patients may experience significant restlessness and anxiety, which may require the use of sedatives for symptomatic control.

Diphtheria-tetanus toxoid vaccine (Adacel, Boostrix, Decavac)

Clinical Context:  Diphtheria-tetanus toxoid vaccine is manufactured by first culturing Clostridium tetani and then detoxifying the toxin with formaldehyde. This toxoid commonly is combined with diphtheria toxoid, and both serve to induce production of serum antibodies to toxins produced by the bacteria.

It is used to induce active immunity against tetanus in selected patients. The immunizing agent of choice for most adults and children older than 7 years are tetanus and diphtheria toxoids. It is necessary to administer booster doses to maintain tetanus immunity throughout life.

Pregnant patients should receive only tetanus toxoid, not a product containing the diphtheria antigen.

In children and adults, it may be administered into deltoid or midlateral thigh muscles. In infants, preferred site of administration is the mid thigh laterally.

Class Summary

Tetanus immunization should be administered following a redback spider bite in all patients who are not already vaccinated, are due for a booster, or whose vaccination status is unknown.

Author

Nathan Reisman, MD, Clinical Assistant Professor, Department of Emergency Medicine, SUNY Downstate Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Disclosure: Nothing to disclose.

Specialty Editors

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

Disclosure: Nothing to disclose.

Matthew M Rice, MD, JD, FACEP, Senior Vice President, Chief Medical Officer, Northwest Emergency Physicians of TeamHealth; Assistant Clinical Professor of Medicine, University of Washington School of Medicine Pending Approval

Disclosure: Nothing to disclose.

Chief Editor

Joe Alcock, MD, MS, Associate Professor, Department of Emergency Medicine, University of New Mexico Health Sciences Center

Disclosure: Nothing to disclose.

Additional Contributors

Robert L Norris, MD, Professor, Department of Emergency Medicine, Stanford University Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Alexandr Rafailov, MD, and Mark A Silverberg, MD, to the development and writing of this article.

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Female redback spider showing a distinctive red stripe over the abdomen. Image courtesy of John Paterson.

Female redback spider with egg sacs. Image courtesy of John Paterson.

Female redback spider showing a distinctive red stripe over the abdomen. Image courtesy of John Paterson.

Female redback spider with egg sacs. Image courtesy of John Paterson.

Female redback spider. Image courtesy of John Paterson.

Female redback spider. Image courtesy of John Paterson.