aka Toxicology Conundrum 003
A 27 year-old woman felt a sting on the back of the right leg while pulling on her tracksuit pants. She investigated further and discovered a small black spider, with a red-stripe on its back, crawling around in her tracksuit pants. A burning itch developed soon after (affecting the back of her right leg) and lasted about an hour.
She then developed pain in the right groin followed by pain in the lower abdomen and then her back. The abdominal and groin pain eventually resolved, but pain developed in both hands, legs and feet some 6 hours after the bite. Sweating first started to affect her right leg but became generalized and was especially profuse over her head and limbs.
Eleven hours after the bite… she presents to your ED.
This case is based on Case 19:2 (page 400) in Sutherland SK and Tibballs J. Australian Animal Toxins – The creatures, their toxins and care of the poisoned patient. (2nd edition). Oxford University Press, 2001.
1. What is the diagnosis?
No not alcohol intoxication….
Redback spider envenoming (aka latrodectism).
2. Describe the clinical features of this condition.
- Redback spider bites are not initially painful.
- Intense local pain develops 5-10 minutes after the bite and is followed by sweating and piloerection within an hour. Puncture marks are not always evident and erythema, if present, is usually mild.
- Systemic envenoming occurs in a significant minority of patients. Pain typically radiates proximally from the bite site to become regional then general (e.g. pelvic, back, abdominal, chest or shoulder pain). Autonomic features include severe sweating which may be regional (e.g. both legs) or generalised, mild hypertension and tachycardia.
- Non‑specific features of envenoming include headache, nausea, vomiting and dysphoria.
- Untreated, systemic envenoming may follow a fluctuating course lasting 1-4 days. Rarely, patients may feel unwell for up to a week. Very rarely, untreated patients report on‑going local symptoms that last weeks or months.
The severity and generalized nature of the pain may mimic an acute abdomen, such as appendicitis, especially in children. In one case report a child with lactrodectism was initially suspected of having tetanus! Lactrodectism should also be suspected in cases of priapism.
3. Name the toxin in Redback Spider venom and describe its mechanism of action.
Redback Spider venom probably contains multiple toxins. The best studied is the vertebrate-specific alpha-latrotoxin, although there are also “latroinsectotoxins” (targeting the spider’s natural prey) and other low molecular weight proteins of uncertain significance.
Skip to the answer for Question 4 if you don’t want to get down and dirty with some biochemical intricacies and speculation…
Alpha-latrotoxin is a high molecular weight (130 kDa) protein that targets neurons and other secretory cells (including endocrine cells) by at least two different mechanisms:
- A mechanism dependent on extracelluar calcium
Alpha-latrotoxin aggregates into tetramers that can form pores in presynaptic neuron cell membranes causing:
- Calcium influx into the cytosol resulting in exocytosis of neurotransmitters (e.g. catecholamines).
- Direct efflux of small intracellular molecules that are important for cell function.
- A mechanism independent of extracelluar calcium
As a monomer alpha-latrotoxin may activate cell-surface receptors such as latrophilin found on neurons.
- Latrophilin (or CIRL: “calcium-independent receptor for latrophilin”) is a G protein-coupled receptor (GPCR) that activates phospholipase C causing:
↑ cytosolic inositol triphosphate (IP3)
→ release of calcium from intracellular stores
→ ↑ exocytosis of neurotransmitters (e.g. glutamate, GABA, acetylcholine).
- Other possible receptors include neurexin Iα and receptor-like protein tyrosine phosphatase σ.
4. What investigations are necessary?
None – it’s a clinical diagnosis.
5. Describe how you would manage this patient.
As per Redback Spider Envenoming:
- Reassure the patient, apply an ice pack and give simple oral analgesia such as paracetamol.
- Do not apply a pressure immobilisation bandage (PIB).
- Refer to hospital if the patient has local symptoms refractory to simple analgesia, clinical features of systemic envenoming, or the diagnosis is in doubt.
Resuscitation and supportive care
- Redback spider envenoming is not life‑threatening and resuscitation is rarely required.
- CSL Redback Spider Antivenom is the definitive treatment of envenoming by spiders of the Latrodectus genus.
- Give an initial two ampoules (2 × 500 units) IV or IM to all patients with systemic latrodectism or local symptoms unrelieved by simple analgesia.
- Give further doses of two ampoules every 2 hours until symptoms are relieved.
I tend to treat with a maximum of 4 ampoules of CSL Redback Spider antivenom, I might go to 6 ampoules if the patient has shown definite but incomplete improvement.
Analgesic techniques other than antivenom that may be used include ice packs, oral analgesia (paracetamol, NSAIDs), and parenteral opiates (e.g. morphine, fentanyl). Their effectiveness is unclear.
The potential role of drugs for neuropathic pain (e.g. amitriptyline, carbamazepine, gabapentin) and regional anaesthetic techniques is yet to be defined.
In real life, all signs and symptoms in this patient were reported to rapidly resolve after the administration of antivenom.
6. Describe the antivenom and the risk of adverse reactions?
CSL Redback Spider antivenom consists of equine-derived purified IgG Fab fragments.
Each ampoule contains 500 units in about 1 mL. This can be administered by intramuscular injection (undiluted) or two ampoules can be diluted in 100 mL normal saline for intravenous administration over 20mins.
CSL Redback Spider antivenom is very safe. Adverse reactions occur in about 2% of cases (intramuscular administration).
- Anaphylaxis (0.5%) is sufficiently rare that no premedication is required but antivenom should be administered in a monitored area with the facilities to manage a possible allergic reaction.
- Serum sickness is also rare (1.68%) but the patient should be informed that they may develop fever, rash, arthralgia, and myalgia typically 5-10 days after the antivenom. No prophylaxis is required as the condition is relatively benign and self-limiting. Patients may be given a “delayed script” of prednisolone (50mg daily for 5 days) or told to see their GP for treatment. It is a good idea to remind the patient to tell any subsequent doctors they see that they have been recently treated with antivenom – otherwise they are liable to be diagnosed with the ‘flu!
- Murray L, Daly FFS, Little M, and Cadogan M. Chapter 5.13 Redback spider and Chapter 6.10 CSL Redback Spider Antivenom; in Toxicology Handbook, Elsevier Australia, 2007. [Google Book Preview]
- Redback Spider Envenoming
- Südhof TC. Alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins. Annual Review of Neuroscience. 2001;24:933-62. [Pubmed]
- Sutherland SK and Tibballs J. Australian Animal Toxins – The creatures, their toxins and care of the poisoned patient. (2nd edition). Oxford University Press, 2001.