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A New Therapy for Brown Recluse Spider Bites

Schulze, Chris MD

doi: 10.1097/01.EEM.0000657636.41011.d9
    brown recluse spider, trichloroacetic acid, TCA. From left: About two, six, and 10 days after Dr. Schulze painted his brown recluse spider bites with TCA.
    Figure
    Figure

    Two spiders are commonly recognized in North America as having medically significant venom: the black widow and its variants (Lactrodectus) and the brown recluse (Loxosceles). The recluse's venom, however, is more indolent and potentially longer-lasting.

    The brown recluse spider is small and rather nondescript, save a violin-shaped marking on its back, and it is reclusive and not aggressive, as its name implies. It is largely found in the south central states, but extends into the Midwest on both sides of the Mississippi Valley.

    The spider is rarely seen before it bites. It stings defensively when it feels threatened, sometimes from the compression of tight clothing or by direct compression. It has very small fangs, so the sting does not penetrate far, and the venom is not deposited deeply in most cases. The envenomation is rarely appreciated when it happens because it is not initially painful and may appear as just a tiny red mark on the skin.

    Most bites are not serious and resolve, but some may progress, subsequently entering an inflammatory phase and finally into the typical expanding necrosis. Some experts believe only about 10 percent of stings go on to necrosis, but the true incidence is unclear given the difficulty of early identification. These factors lead to delays in treatment. By the time the lesion can be identified as a brown recluse bite, it is already into the long-lasting ulcerative phase with ever-enlarging skin necrosis.

    Traditional Treatment

    Treatment historically has been wide surgical resection for larger, deeper, non-healing lesions because it has been long recognized that some component in the venom (known to contain phospholipase D and sphingomyelinase) is persistent in the tissue, continuing to induce new necrosis. (Toxicon. 2016;120:97; http://bit.ly/37dHLys; J Invest Dermatol. 2005;124[4]:725; http://bit.ly/30Ea6f0.) The mechanism of the necrosis is by neutrophil aggregation with untargeted release of necrotizing enzymes.

    A paper from the University of Arizona identified a particular enzyme in the venom that cleaves the heads off long fatty acids and then connects the ends to form large cyclo-alkanes, which may be proinflammatory and may be the persistent cause of the enlarging necrosis. (PloS ONE. 2013;8[8]:e72372; http://bit.ly/2ujyVAQ.) These large ring-structures, to my knowledge, are not usually found in biosystems and may persist due to lack of any intrinsic system for their disposal. Chemically, they are quite stable in contrast to the original foreign protein enzyme, which should be gradually degraded if it is recognized as foreign (as well as the usual, natural slow degradation of these large proteins).

    Attempts at medical therapy through immunomodulation have had some positive effects in delaying necrosis—thalidomide in early trials, dapsone more recently. (Am J Emerg Med. 2003;21[1]:420.) But these agents used alone have generally been ineffective in changing the final outcome. Other medical treatments, including antihistamines and antibiotics for secondary infection, have been proposed, they generally lack good data to back them.

    Experimental specific antivenin exists as a research tool, but is not commercially available. Watchful waiting and local wound care may be appropriate, but most patients are not pleased to see an expanding necrotic lesion and are not patient enough for conservative care. Surgery has fallen out of favor in most instances, but surgery with wide excision remains the definitive treatment for larger non-healing or infected lesions, though it can leave significant scarring.

    Personal Experience

    I was stung by brown recluse spiders, probably juveniles, on both antecubital areas while spring cleaning at a rural property in Texas in 2016. Initially, I had nonspecific small red lesions, but they were followed by a large inflammatory response and subsequent ulceration. I conferred with a more knowledgeable colleague, and she confirmed that the lesions appeared to be typical for brown recluse envenomations.

    I elected to self-treat with daily debridement, but the lesions continued to enlarge. There was not much pain, but the itching was intense and only partially and temporarily relieved by topical lidocaine and NSAIDs. Narcotics were more effective, but I avoided them. One night, awakened by the itching, I went to my medicine cabinet looking for relief. I noticed a bottle of trichloroacetic acid (TCA; 50%) that I had previously used to remove a small skin lesion.

    Recalling that it caused tingling and stinging, I painted the edges of the right arm ulceration, and felt almost immediate cessation of the itching. More surprisingly, the ulceration stopped expanding over the next few days and eventually healed (without scarring) over the next several weeks. I then conducted a trial on the left arm, painting half the lesion. About 10 days later, I painted the remaining area. This lesion also healed without scarring.

    About a year later, I suffered more envenomations at my home, again while cleaning outside. Multiple lesions formed on my arms and along my waistline. (Am J Emerg Med. 2003;21[1]:420.) I treated the arm lesions with TCA when they started to ulcerate, and that arrested the progression. I treated the smaller waistline lesions early, and they resolved with immediate relief of the itching and without ulceration. Since then, I have had the misfortune to be stung yet again by a brown recluse. Early application of TCA immediately relieved the discomfort and itching and prevented ulceration.

    More Stings

    I have also been stung by a common black jumping spider, a bumblebee, and mosquitoes, all of which have protein-based components in their bites and stings. Applying TCA completely relieved the effects of these envenomations in a matter of seconds. (Curiously, the mosquito bites stung more intensely for about 15 seconds before total relief.) I have also tried TCA on fire ant bites, and as expected, it had no effect. The venomous components of fire ant bites are piperidine derivatives called solenopsins rather than proteinaceous enzymes.

    These experiences prompted me to do considerable research on TCA. It is a triple chlorine-substituted acetic acid molecule. It has long been used in minor cosmetic procedures to elicit a mild to moderate skin peel. The TCA penetrates the top skin layers, attacking the cell membranes beneath and causing a sloughing of the outer layer. Depth is associated with the volume of TCA applied. YouTube has multiple videos explaining do-it-yourself techniques. It is quite safe when used in moderation and according to guidelines. Over-application can lead to marked skin destruction, ulceration, and scarring. Medical professionals use it for skin peels of moderate depth, as opposed to the deeper phenol-based peels.

    But there is another bioapplication for TCA; it is commonly used in laboratories to coagulate and denature proteins. The effect is well documented, and the amounts required are directly related to the volume of protein available.

    I propose that TCA is able to denature the offending protein-based toxin directly, rendering it ineffective by virtue of its ability to penetrate the top layers of the skin and its protein coagulation properties. If the cycloalkanes are a component in toxicity, there may be some additional effect of simple substitution of chlorine for hydrogen in the cycloalkanes or with the phosphate portion of the molecule, which may make the rings unstable or cause enough change that they are subject to other destructive processes.

    This treatment may be useful for other protein-based envenomations if it is found to be effective and safe. Here in the southern United States, we also have a nasty moth caterpillar, locally called the asp or pussy caterpillar, which inflicts a painful sting via tiny spines on its hairy projections. The pain from these is notoriously difficult to treat, but the venomous component is known to be a protein-based enzyme and the envenomation is superficial, a perfect candidate for TCA. Likewise, jellyfish stings are by tiny nematocysts that inject protein and peptide toxins into the skin, providing another possible substrate for TCA. TCA's physical properties, with modification of the delivery system, may even have some application for deeper envenomations, especially if suitable antivenin is not available or if there could be a delay in treatment.

    TCA Caveats

    TCA, while quite safe when used appropriately, is not without danger. It is extremely corrosive to living tissue when used in excess, and it should only be painted onto the skin with a cotton swab. Direct application is not recommended. I have noticed that the 50% TCA that I used acted as a surfactant or wetting agent, allowing a marked spread along tissue planes. A 30-microliter aliquot expands to an area of about 1-1.5 cm in diameter, which makes direct application a blunt treatment modality, potentially affecting a much larger area than intended.

    Some literature expresses concern that TCA is carcinogenic, but I have not been able to find any specific documentation of this allegation. The fact that it is readily available and already used in direct patient treatment attests to its safety when used in a controlled manner. Allergenicity should be low because TCA is a polysubstituted small molecule, of which the parent analog (acetic acid) is common in living organisms.

    A double-blind study would take a very long time and would be fraught with uncertainties from the start, largely because of the sporadic nature of brown recluse bites. TCA is relatively innocuous when used appropriately, and I encourage other practitioners to try this technique on possible brown recluse bites. Patients should be made aware that mild skin peeling occurs five to 10 days after application. Please share your experience by writing to me at emn@lww.com.

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    Dr. Schulzeis an emergency physician in Houston.

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