Funnel Web Spider Envenomation

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Background

Australian funnel-web spiders (family Hexathelidae, subfamily Atracinae, genera Atrax and Hadronyche) are among the most venomous spiders in the world based on clinical experience in Australia,[1, 2] although their importance to human health is limited by their confined geographic range.[3] Funnel-web spiders belong to the suborder Mygalomorphae, a primitive group of spiders that also includes tarantulas. Funnel-web spiders of medical importance comprise 40 species within 2 genera, Atrax and Hadronyche, in the family Hexathelidae, subfamily Atracinae. The Atrax genus contains 3 species, including Atrax robustus, the Sydney funnel-web spider. The remaining 37 species are members of the genus Hadronyche. Funnel-web spiders are primarily found on the eastern coast of Australia. Related funnel-web spiders can also be found in New Guinea and the Solomon Islands.

Funnel-web spiders are medium-to-large robust spiders that tend to be dark or black in color. These spiders measure up to 5 cm. They have stout legs and prominent fang-bearing chelicerae that deliver a neurotoxic venom. The common name derives from the funnel-like entrance to silk-lined subterranean burrows built by both males and females. The Sydney funnel-web spider (A robustus) is responsible for most reported envenomations and the only confirmed deaths in humans.[4, 5] The Sydney funnel-web spider is shown in the image below.



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The Sydney funnel-web spider, Atrax robustus. Male (left) and female (right). Photograph courtesy of the Australian Venom Research Unit, Department of....

However, bites from other funnel-web spiders, particularly the northern tree spider, Hadronyche formidabilis, are likely to cause serious envenomation syndromes and are potentially deadly if untreated.

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

Bites from funnel-web spiders are rare. In Australia, a total of 138 funnel-web spider bites have been documented from 1926-2004.[1] A prospective study revealed only 16 envenomations between 1999 and 2003[6] ; 10-20% of bites produce toxicity. Male funnel-web spiders exhibit a seasonal wandering behavior in search of female mates, which often brings them into houses and in contact with humans. As a result, male spiders are responsible for most bites. Unfortunately, the venom of male spiders is apparently more toxic than that of female spiders. Humans and other primates suffer severe life-threatening toxicity from the venom, while other vertebrates, such as rabbits and cats, are almost unaffected. Only 13 fatalities have been attributed to the bite of a funnel-web spider.[1] No fatalities have occurred since the introduction of an effective antivenin in 1981.[1, 3]

Pathophysiology

The venom component responsible for mortality and morbidity is a single peptide known as delta-hexatoxin (formerly delta-atracotoxin).[7, 8] Funnel-web spider antivenom, derived from purified immunoglobulin G (IgG) of rabbits hyperimmunized with A robustus venom , is also effective against venom of Hadronyche species. Delta-hexatoxins are polypeptide neurotoxins that induce spontaneous, repetitive firing and prolongation of action potentials in presynaptic autonomic and motor neurons.[9, 10]

Delta-hexatoxin binds to the outer surface of tetrodotoxin-sensitive sodium channels. After binding, they induce excitability of these voltage-dependent sodium channels. The toxins also interfere with the conformational changes necessary for gating and inactivation of the channel. The ensuing massive neurotransmitter release results in an autonomic storm. The excessive release of endogenous acetylcholine, norepinephrine, and epinephrine is responsible for many of the clinical findings of funnel-web spider envenomation.

Envenomation is heralded by substantial pain at the bite site.[1] Most funnel-web spider bites do not proceed to severe systemic symptoms, causing only mild or local neurotoxic effects. In severe cases, the onset of symptoms is rapid, with a median onset of 28 minutes.[1] Agitation and vomiting are common. Autonomic effects include diaphoresis, salivation, piloerection, lacrimation, and pupillary changes. Cardiovascular changes commonly include hypertension and tachycardia. Hypotension and bradycardia occur more rarely. Pulmonary edema can occur in severe envenomations, with dyspnea and pink, frothy sputum often accompanied by respiratory failure. Skeletal muscle fasciculation, muscle spasms, and oral paresthesias are frequent neurologic findings. Coma or loss of consciousness occurs in about 10% of patients who experience severe envenomation.

Epidemiology

Frequency

Funnel-web spiders of medical importance are found in eastern and southern Australia.[11] The Sydney funnel-web spider (A robustus) is distributed in a roughly 75-mile radius around the city of Sydney. Hadronyche species have a much wider distribution, from southeast Queensland to Victoria, Tasmania, and parts of South Australia.

Sixteen confirmed cases of funnel-web spider bites were reported to poison control centers or hospitals in Australia from 1999-2003. A minority of patients (10-20%) require treatment with antivenom.[6]

Age

Bites are equally common in adults and children. However, envenomation in children is more severe because of the greater venom load per kilogram of body mass. Children may experience life-threatening envenomation within an hour of the bite and require immediate treatment.

Prognosis

Only 1 in 10 people bitten by a funnel-web spider displays signs of envenomation; however, if envenomation occurs, mortality rates are high in patients who receive no antivenom treatment. Most patients who survive until antivenom can be administered are able to make a complete recovery.

The mortality rate is difficult to determine from data from the era before antivenom. From 1927-1980, 13 deaths attributed to A robustus were reported in the medical literature and news media. No deaths have occurred since the introduction of antivenom.[1]

Deaths occurred in children and adult females with bites. In all cases where the spider was identified, the culprit was the Sydney funnel-web spider, A robustus. Severe envenomation, but not death, has been reported following bites by Hadronyche species.

Death occurs between 15 minutes and 3 days following the bite. In children, death is usually early and caused by pulmonary edema. In adults, death usually occurs later and is caused by persistent hypotension and cardiovascular collapse. In the late 1970s, 2 deaths occurred despite modern intensive care units. Death in these cases occurred from multisystem organ failure days after the bite.[12]

History

The spider usually is seen, and its bite is extremely painful for hours to days (the fangs are large and enter with considerable force). Early symptoms of systemic envenomation may occur rapidly, with a 28-minute median onset. A pressure-immobilization dressing can delay onset of symptoms.

The following are symptoms of a serious envenomation:

Physical Examination

Erythema, piloerection, diaphoresis, and muscle fasciculation may be seen at and around the bite site.

Generalized diaphoresis, lacrimation, and salivation may be noted.

Fasciculations and muscle spasms are frequent findings in severe envenomation; however, paralysis does not appear to occur.

A brief period of hypotension and tachycardia is followed by severe hypertension.

Cardiac arrhythmias and cardiac arrest may occur.

Severe pulmonary edema that is poorly responsive to loop diuretics occurs early and may be fatal.

Laboratory Studies

No assay is available for the clinical detection of funnel-web spider venom.

Perform laboratory studies to assess the effects of envenomation or in consideration of differential diagnoses and coexistent conditions.

Obtain arterial blood gas measurements, serum electrolyte levels, and creatinine clearance to assess for hypoxia, acidosis, hyperglycemia, and renal impairment.

Measure serum glucose level in any patient with altered mental status to exclude hypoglycemia.

Elevated serum creatine kinase can indicate rhabdomyolysis and should be measured.

CBC count results may demonstrate hemoconcentration, and coagulation studies may demonstrate a coagulopathy.

Imaging Studies

A chest radiograph may demonstrate pulmonary edema.

Prehospital Care

If possible and when expedient and safe, the spider should be killed and collected for identification.

A pressure immobilization bandage identical to that applied in the management of Australian snakebite should be applied immediately.[13] The dressing prevents migration of venom via lymphatics to the central circulation. Simultaneous immobilization (with a splint and/or sling) diminishes the muscle-pump effect on lymphatics and venous flow. Tourniquets are to be avoided.

Pressure immobilization must be maintained until the patient arrives at a hospital where antivenom is available.

Supportive care, including cardiac and respiratory life support, should be performed as necessary and according to the advanced cardiac life support (ACLS) protocol.

Emergency Department Care

Most bites do not result in severe envenomation, although local pain at the site of the bite is common. When severe envenomation occurs, resuscitation measures and antivenin therapy should be instituted as necessary.

Funnel-web spider antivenom (CSL, Melbourne) is prepared by hyperimmunizing rabbits with the venom of A robustus. It has been effective in treating victims of a variety of species of Australian funnel-web spiders. Antivenom has been highly successful in the treatment of A robustus envenomation. Complete resolution of symptoms has occurred in 97% of patients treated with antivenom after confirmed funnel-web spider bites. Antivenom has been used successfully in pregnant women, breastfeeding women, and children. Anaphylaxis is a risk when giving antivenom. In a recent review, adverse effects consistent with anaphylaxis occurred in 2 patients of 75 treated with antivenom. One patient of the 75 developed serum sickness within 7 days of administration of antivenom.[1]

Premedication with an antihistamine and steroid to prevent anaphylaxis may be considered. However, premedication with epinephrine is contraindicated because of elevated catecholamine levels induced by the venom. Administration of epinephrine is appropriate if anaphylaxis occurs. Antivenom should be given in the ED or intensive care unit with close monitoring by medical and nursing staff. The initial dose of antivenom is 2 bottles intravenously, but most cases require 4 or more bottles.

Antivenom is indicated if any of the following are present:

As with any bite, ensure that tetanus immunization status is up to date.

Inpatient Care

Patients who respond to antivenom may be discharged within a day or so if no complications occur.

Management is more difficult if antivenom is unavailable; in such cases, the patient may need to spend many days in intensive care.

Important insights into management before the availability of antivenom have been provided by Fisher et al.[12]

Prolonged ventilation in the intensive care unit may be required for treatment of respiratory failure. Adequate sedation is essential.

Atropine has been used to provide parasympathetic blockade.

In the early stages, hypertension may be treated with alpha-blockers, but massive doses may be required.

Reversible agents are preferred because of the possible development of hypotension as envenomation progresses.

Theoretically, beta-blockade may be lethal (because of unopposed alpha-stimulation) and is not advocated.

Consultations

Referral to an intensive care specialist may be necessary in cases of moderate-to-severe envenomation.

Advice from an experienced toxicologist practicing in an endemic area (eg, Sydney, Newcastle) should be sought in all funnel-web spider bites.

The New South Wales Poisons Information Centre has toxicologists available 24 hours a day.

Complications

Once successfully treated with antivenom and recovered from the acute illness, patients are unlikely to experience further complications. As with all patients receiving antivenom, the patient should be advised to seek medical care if signs of serum sickness occur.

Long-Term Monitoring

Routine follow-up is not required; however, the theoretical risk of serum sickness caused by the foreign protein load of antivenom mandates that the patient be advised to report symptoms. Nevertheless, serum sickness has not yet been reported following treatment with funnel-web spider antivenom.

Medication Summary

Pharmacologic therapy is indicated for patients with severe envenomations.

Funnel-web spider antivenom

Clinical Context:  This is freeze-dried IgG prepared from rabbit serum, reconstituted with water for injection, and dispensed in bottles of 125 Units. It should be administered only where appropriate resuscitation facilities are immediately available. Antivenin may not be commercially available at most pharmacies.

Class Summary

This agent neutralizes the toxins from the spider bite.

Atropine IV/IM

Clinical Context:  Atropine is used for the relief of excessive airway secretions.

Class Summary

These agents are indicated when symptoms of salivation and copious airway secretions compromise a victim's ability to breathe.

Author

Joe Alcock, MD, MS, Associate Professor, Department of Emergency Medicine, University of New Mexico Health Sciences 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 Emeritus, 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 author, Simon G A Brown, MBBS, PhD, FACEM, to the development and writing of this article.

References

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  2. Wong MKL, Woodman JD, Rowell DM. Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider. Ecol Evol. 2017 Jul. 7 (14):5094-5102. [View Abstract]
  3. Isbister GK, Fan HW. Spider bite. Lancet. 2011 Dec 10. 378(9808):2039-47. [View Abstract]
  4. Al-Agroudi MA, Ahmed SA, Morsy TA. INTERVENTION PROGRAM FOR NURSING STAFF REGARDING APPROACH TO A PATIENT WITH SPIDER PHOBIA AND/OR BITE. J Egypt Soc Parasitol. 2016 Apr. 46 (1):167-78. [View Abstract]
  5. Hedin M, Derkarabetian S, Ramírez MJ, Vink C, Bond JE. Phylogenomic reclassification of the world's most venomous spiders (Mygalomorphae, Atracinae), with implications for venom evolution. Sci Rep. 2018 Jan 26. 8 (1):1636. [View Abstract]
  6. Isbister GK, Gray MR. Bites by Australian mygalomorph spiders (Araneae, Mygalomorphae), including funnel-web spiders (Atracinae) and mouse spiders (Actinopodidae: Missulena spp). Toxicon. 2004. 43(2):133-40. [View Abstract]
  7. Pineda SS, Wilson D, Mattick JS, King GF. The lethal toxin from Australian funnel-web spiders is encoded by an intronless gene. PLoS One. 2012. 7(8):e43699. [View Abstract]
  8. Windley MJ, Vetter I, Lewis RJ, Nicholson GM. Lethal effects of an insecticidal spider venom peptide involve positive allosteric modulation of insect nicotinic acetylcholine receptors. Neuropharmacology. 2017 Dec. 127:224-242. [View Abstract]
  9. Graudins A, Wilson D, Alewood PF, Broady KW, Nicholson GM. Cross-reactivity of Sydney funnel-web spider antivenom: neutralization of the in vitro toxicity of other Australian funnel-web (Atrax and Hadronyche) spider venoms. Toxicon. 2002 Mar. 40(3):259-66. [View Abstract]
  10. Miller M, O'Leary MA, Isbister GK. Towards rationalisation of antivenom use in funnel-web spider envenoming: enzyme immunoassays for venom concentrations. Clin Toxicol (Phila). 2016 Mar. 54 (3):245-51. [View Abstract]
  11. Isbister GK, Gray MR. A prospective study of 750 definite spider bites, with expert spider identification. QJM. 2002 Nov. 95(11):723-31. [View Abstract]
  12. Fisher MM, Carr GA, McGuinness R, Warden JC. Atrax robustus envenomation. Anaesth Intensive Care. 1980 Nov. 8(4):410-20. [View Abstract]
  13. Sutherland SK, Duncan AW. New first-aid measures for envenomation: with special reference to bites by the Sydney funnel-web spider (Atrax robustus). Med J Aust. 1980 Apr 19. 1(8):378-9. [View Abstract]

The Sydney funnel-web spider, Atrax robustus. Male (left) and female (right). Photograph courtesy of the Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Australia.

The Sydney funnel-web spider, Atrax robustus. Male (left) and female (right). Photograph courtesy of the Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Australia.

Female funnel-web spider. Image courtesy of Glenn DuBois, CEO, http://www.termite.com/spider-identification.html.

Male funnel-web spider. Image courtesy of Glenn DuBois, CEO, http://www.termite.com/spider-identification.html.