aka Toxicology Conundrum 004
Reviewed and Revised 25 August 2012
You are called by Doctor X working in Osaka, Japan.
Doctor X has just assessed a 44 year-old male who thinks he was bitten or stung by something under his house three days ago. The initial discomfort was mild and localized to his right forearm. However the pain traveled up his arm over the next few hours. Since then he has had pain in his arms and back, nausea, headache, and diaphoresis (sweating). On examination he has mild erythema (redness) on his right forearm, with “goose pimple” skin and tackiness on palpation.
Doctor X is asking for help with the diagnosis and management of this case.
Q1. This sounds like a Redback spider envenoming… is that possible?
When and where do Redback spider bites tend to occur?
Redback spiders have been found in Osaka since 1995; they have also been found in other areas of Japan creating a degree of public hysteria.
Although I am not aware of any reports of cases of redback spider envenoming in Japan, antivenom derived from Australian Redback spider venom is stocked in places like Osaka. Interestingly, the antivenom appears to bind the venom of other species of Lactrodectus also found in Japan [abstract].
Redback spiders were probably introduced to Australia in the 1870s and today bites occur throughout the country. Bites are more likely in the warmer months and peak between January and April.
Redback spiders have the potential to colonise other temperate areas of the world… so watch out!
Redback spiders live in dark or dry areas. Bites tend to occur when people are putting on shoes or when they are moving outdoor pot plants, furniture, or firewood. A favourite hiding place is under the seat in an outdoor “dunny” (toilet)…
Q2. How severe is the pain after Redback spider bites?
“Severe and persistent pain” occurs in over half of cases, and is “severe enough to prevent sleep” in a third of cases.
Oral analgesics and ice packs are unlikely to be sufficient unless envenoming is mild. In severe cases parenteral opiates may not be effective.
Q3. Who should get antivenom? Is it too late to give antivenom in this case?
Antivenom should be given for:
- Severe local pain or radiating pain, particularly if refractory to other analgesic measures.
- Systemic envenoming.
Doctors sometime agonise over whether to give antivenom. I like to involve the patient in the decision-making process. I tell them about “BRAN“: benefits, risks, alternatives, and what happens if we do nothing. Incidentally, antivenom has been safely used in pregnant and breast-feeding women.
If the patient declines antivenom for any reason that’s usually OK – envenoming is not lethal, and the patient can always change their mind and get treatment later.
Generally, antivenom is indicated if the patient has systemic features such as:
- pain spreading to parts of the body other than the bitten limb
- distressing anxiety or dysphoria
- nausea or vomiting
- generalized autonomic features (e.g. diaphoresis, tachycardia, or hypertension)
Redback spider envenoming can follow a fluctuating course over about 4 days, and rarely patients may be systemically unwell for up to a week. Given this natural history and anecdotal reports of effectiveness, antivenom should be considered up to 96 hours after the bite.
In this case, I would offer the patient treatment with Redback Spider antivenom.
Q4. What is the preferred route of antivenom administration?
The answer to this question remains controversial.
Although the recent RAVE study suggests that:
“the difference between IV and IM routes of administration of widow spider antivenom is, at best, small and does not justify routinely choosing one route over the other.”
My practice is to treat with intravenous (IV) antivenom, rather than intramuscular (IM), in most cases.
I advise this because:
- The RAVE study of 126 patients did show some difference for a reduction in pain at 2 hours:
- “the probability of a difference greater than zero (IV superior) was 85%”
- although, admittedly, the difference is likely to be small because “the probability of a difference >20% was only 10%”.
- In the small trial of 31 patients by Ellis et al (2005):
- IV and IM administration were equivalent for relief of pain at 2 hours (the study was underpowered)
- BUT at 24 hours the IV group were more likely to be pain-free (76% vs. 21%; 95% CI 25-85% difference).
- Logically, IV shouldwork faster.
- In volunteers IV antivenom is detectable in serial blood sampling within 30 minutes, IM takes a median of 3.2 hours.
- IV administration has a low reaction rate – Isbister (2007) showed that:
- 4 of 92 patients had immediate systemic hypersensitivity reactions (none severe).
- 3 of 32 patients followed for 2 weeks had serum sickness.
- IV administration can be slowed or stopped in the event of an adverse reaction.
Q5. Rumour has it that antivenom might not work – is this true?
It is possible that redback antivenom is ineffective.
Anecdotally, most clinicians in Australia experienced in using CSL Redback spider antivenom have seen good responses to administration in envenomed patients.
However, the authors of the RAVE study comment that “antivenom may provide no benefit over placebo”. All I can say is “roll on RAVE 2!”, which will compare antivenom with placebo…
In the past many redback spider envenomings were treated with just one ampoule of antivenom. More recently, sometimes up to a dozen or more ampoules were used in severe cases. We have now moved to a middle ground. Why one ampoule no longer seems to be effective is unclear. Has the antivenom changed? Has the venom changed? Have doctors changed?
Finally, I’ve finally found a recording of “Redback on the Toilet Seat” by Slim Newton – great intro…
References and Links
- Murray L, Daly FFS, Little M, and Cadogan M. Chapter 3.44 Mercury; in Toxicology Handbook, Elsevier Australia, 2007. [Google Book Preview]
- Redback Spider Envenoming
- Isbister GK, O’Leary M, Mark Miller, et al. A comparison of serum antivenom concentrations after intravenous and intramuscular administration of redback (widow) spider antivenom. British Journal of Clinical Pharmacology 2008; 65, 139-143. [Pubmed]
- Isbister GK, Gray MR. Latrodectism: a prospective cohort study of bites by formally identified redback spiders. Medical Journal of Australia 2003; 179:88-91. [Fulltext]
- Isbister GK, Brown SG, Miller M, et al. A randomised controlled trial of intramuscular vs. intravenous antivenom for latrodectism – the RAVE study. QJM. 2008; 101:557-65. [Pubmed]
- Ellis RM, Sprivulis PC, Jelinek GA, et al. A double-blind, randomized trial of intravenous versus intramuscular antivenom for Red-back spider envenoming. Emergency Medicine Australasia 2005; 17, 152-156. [Pubmed]
- Isbister, GK. Safety of IV administration of redback spider antivenom. Internal Medicine Journal 37 (2007) 820-822 [Abstract]
- Also check out Toxicology Conundrum 003