Funnel-Web Spider Toxicity

Etiology

FWSs consist of 36 Australian species classified based on anatomical differences and 38 related non-Australian species in the genus Macrothele. Most FWSs are ground-dwelling, including the well-known species Atrax robustus (Sydney FWS) and Hadronyche infensa (Toowoomba FWS). Tree-dwelling species include the Hadryonyche cerberea (Southern tree-swelling FWS) and Hadronyche formidabilis (Northern tree-dwelling FWS).[4][5] Data suggest that tree-dwelling species are associated with much higher rates of severe envenomations than ground-dwelling FWSs. Of these spiders, only 6 species have been identified as containing δ-hexatoxins.[6]

All FWS bites should be treated as potentially life-threatening, even though only 10% to 15% are venomous. Since the venom from an FWS bite is highly toxic, all species should be considered potentially dangerous.[7] In all the fatalities where the spider's gender was confirmed, the male FWS was responsible. Male FWSs are more active at night and are known to enter homes.

The onset of severe envenomation is rapid. A study revealed that the median time to envenomation was 28 minutes. Only 2 cases had an onset longer than 2 hours, with pressure immobilization bandages applied to the bites in both cases. Death may occur within 15 minutes in small children and within 3 days in adults. Younger patients and those with underlying medical conditions have a higher fatality risk after an FWS bite.

Epidemiology

Published data concerning FWS envenomation is lacking. A 2005 systematic review identified 198 potential FWS bites from 1999 to 2003. Of these cases, 138 were confirmed as FWS bites, and 77 resulted in severe envenomation. Severe envenomations were attributed to 3 species restricted to New South Wales and southern Queensland: Hadronyche cerberea (75%), H formidabilis (63%), and Atrax robustus (17%). Antivenom was used in 75 patients, including 22 children, producing a complete response in 97% of the positively identified cases.

The FWS antivenom produced 3 adverse reactions: early mild systemic inflammation, early severe inflammation requiring epinephrine, and delayed serum-sickness reaction. The researchers concluded that severe FWS envenomations were confined to New South Wales and southern Queensland, with the tree-dwelling FWSs having the highest envenomation rates. The FWS antivenom was deemed safe and effective and rarely produced severe allergic reactions. True necrotizing arachnidism appeared to be quite rare.

Pathophysiology

The venom of FWSs is complex, containing thousands of peptide toxins. Among these, the δ-hexatoxins are primarily responsible for symptomatic envenomation.[8][9][10] Specifically, the δ-atracotoxins robustotoxin (Ar1) and versutoxin (Hv1a) are amino acid peptides with 42 to 44 residues and 4 disulfide linkages.[11][12] These neurotoxins have highly preserved homologous sequences and activity in mammals and insects.[13]

Atracotoxins bind to the S3/S4 loop of voltage-gated sodium channels' domain IV. This loop is responsible for the conformational change that inactivates the sodium channels.[14] Atracotoxin binding prevents this conformational change, prolonging action potentials. Continuous firing increases neurotransmitter release in autonomic and somatic nerve synapses, leading to neuroexcitation. The neurotransmitters involved include acetylcholine, norepinephrine, and epinephrine. Envenomated patients present with localized pain progressing to muscle fasciculations, hypertension, gastrointestinal distress, and cardiac dysrhythmias.[15][16]

History and Physical

Patients concerned about an FWS bite should be asked if they saw the spider that bit them. If a patient does not describe seeing a "big black spider," then FWS envenomation is less likely. A redback spider, also known as the Australian black widow, is also black but has a large red mark on its back. When evaluating the patient, the bite's geographic location should be considered.

FWS envenomation is a differential diagnosis in an individual presenting with unconsciousness, apnea, and pulselessness—signs indicative of a cardiopulmonary arrest. A quick primary survey assessing airway, breathing, and circulation is warranted in such cases. Resuscitative measures must be initiated immediately if these symptoms persist despite verbal and tactile stimulation. After stabilization, a more detailed secondary survey may be pursued.

Early FWS envenomation symptoms include facial paresthesias, nausea, vomiting, profuse diaphoresis, drooling, and shortness of breath. Patients may become agitated, confused, and ultimately comatose. Bites are associated with autonomic derangements, including hypertension, tachycardia, metabolic acidosis, dilated pupils, muscle twitching, and pulmonary and cerebral edema. Death results from pulmonary edema or progression to hypotension and circulatory collapse.[17] Symptom onset is typically within minutes but can be delayed by several hours by measures such as pressure immobilization.

Physical examination may reveal fang marks in the area of pain with or without bleeding. The bite is not typically associated with significant edema or erythema. Patients may develop cardiovascular and neurologic complications from an FWS bite. These parts of the physical examination must be thoroughly documented to guide proper management.

Evaluation

Eliciting a history of acute cardiovascular and neurologic changes after being bitten by an FWS or finding the spider bite on physical examination in an endemic area can help arrive at the diagnosis of FWS envenomation. No laboratory assay is available specifically for FWS venom detection. However, laboratory evaluation can rule out other conditions and assess the severity of end-organ damage if present. Testing should include a complete blood count, a basic metabolic panel, and serum creatinine kinase to assess kidney function, electrolyte abnormalities, and the presence of rhabdomyolysis. Arterial and venous blood gas results can help determine acid-base derangements. Coagulation studies should be used to evaluate for signs of disseminated intravascular coagulation. Other testing may include troponin, electrocardiogram, and chest x-ray. 

Treatment / Management

Initial Care

FWS envenomation can cause severe symptoms that can worsen and progress rapidly. All bites from large, dark-colored spiders in endemic areas should be treated as FWS bites. The first-aid treatment for suspected FWS bite poisoning consists of cleansing the bitten area with soap and tap water, followed by applying a pressure-immobilization bandage. This technique entails applying a light-pressure bandage and immobilizing the affected area as if it were being splinted. Pressure immobilization limits the venom's lymphatic flow and systemic spread, minimizing the venom-affected area. Evidence suggests that pressure immobilization leads to local FWS venom inactivation.[18](B3)

Emergency medical treatment should be sought immediately after an FWS bite. Maintaining the pressure-immobilization bandage is critical until the patient is evaluated by trained medical personnel in an emergency department. Premature pressure-immobilization bandage removal can cause rapid systemic venom mobilization, leading to rapid deterioration. Thus, intravenous access should be established, and the patient should be connected to the appropriate cardiorespiratory monitoring equipment before removing the pressure-immobilization bandage. Antivenom should be prepared before bandage removal.

Antivenom administration is the primary treatment for systemic FWS envenomation. Other supportive measures may be indicated. Antivenom should be given at the earliest sign of systemic envenomation. Patients without systemic symptoms should be monitored closely for 4 to 6 hours from the time of envenomation or pressure-bandage removal if applied immediately after the FWS bite. Antivenom is not indicated if the patient only has localized symptoms after an appropriate observation period. Patients who do not develop systemic symptoms after this observation period can be discharged.

Patients should be given analgesics for pain. Opioid pain medications are often required.

Antivenom

FWS antivenom (FWSAV) was developed in 1981 and has successfully treated severe envenomation in numerous patients.[19] Antivenom consists of rabbit IgG against Atrax robustus venom. One ampule contains 100 mg of purified IgG or 125 units of neutralizing capacity. Initial dosing consists of 2 ampules if systemic signs are present and 4 ampules if acute respiratory distress syndrome or mental status changes ensue. Doses should be repeated every 15 minutes until clinical improvement. Some patients may require up to 8 ampules.(B3)

Evidence suggests that 2 ampules may be sufficient to bind all free venom, and continued systemic symptoms may be due to irreversible effects.[20] Serum sickness from the antivenom is rare, and anaphylaxis has not been reported. FWSAV has proven effective against several different FWS species and is recommended for use in envenomation from most Australian FWS species.[21]

Differential Diagnosis

The differential diagnosis for FWS bites includes other arthropod bites, cutaneous abscesses, and cellulitis. Other differentials in patients with systemic symptoms include acute coronary syndrome, anaphylaxis, congestive heart failure, organophosphate exposure, nerve agent exposure, or medication overdose. An adequate history and physical examination help determine the likelihood of FWS envenomation.

Prognosis

FWS envenomation can be fatal if untreated. Most confirmed FWS bites are dry and result in only local reactions from the bite itself. However, the potentially life-threatening nature of FWS envenomation warrants a low threshold for antivenom treatment after an FWS bite unless a complete medical examination has ruled out the condition. Antivenom is the standard of care for patients with systemic symptoms. The FWS antivenom can reverse the systemic toxicity if administered early, allowing patients to make a full recovery.

Complications

Most patients who develop systemic toxicity from an FWS bite who received antivenom make a full recovery. Complications depend on the affected organ systems and may include:

• Rhabdomyolysis
• Kidney failure
• Cerebral edema
• Acute respiratory distress syndrome
• Respiratory failure
• Cardiac dysrhythmias leading to cardiac arrest
• Anoxic brain injury

Pressure-immobilization bandage application and immediate medical intervention can prevent rapid systemic progression and the development of complications.