The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.

Brown Recluse Spider Bites in Patients With Neutropenia: A Single-institution Experience.

Brown recluse spider bites can cause local and systemic signs, including rash, dermonecrosis, edema, hemolysis, and acute kidney failure. These are mostly attributed to sphingomyelinase D, the main toxin. To evaluate the severity of the disease in pediatric patients with and without neutropenia, we retrospectively reviewed records of patients treated at St. Jude Children's Research Hospital between 1970 and 2015 and identified 19 patients who met the inclusion criteria. Variables of interest included the type of underlying illness, presence of neutropenia, number of days of hospitalization, disease signs and outcome of the bite, and treatments administered. We used descriptive statistics to summarize the manifestations and severity of spider bites in patients with and without neutropenia. Six patients experienced pain from the bite, 11 had erythema, 7 developed edema, and 5 had fever. The response to spider bites in neutropenic patients was no milder than that in non-neutropenic individuals. Six patients developed systemic complications. Compared with non-neutropenic patients, neutropenic patients had antibiotics prescribed more often and experienced longer hospital stays. Spider bites do not seem to have a different clinical course in neutropenic patients. Therefore, a conservative approach may be best for these patients, with close monitoring and local wound care.

Targeting Loxosceles spider Sphingomyelinase D with small-molecule inhibitors as a potential therapeutic approach for loxoscelism.

Loxosceles spiders' venoms consist of a mixture of proteins, including the sphingomyelinases D (SMases D), which are the main toxic components responsible for local and systemic effects in human envenomation. Herein, based on the structural information of SMase D from Loxosceles laeta spider venom and virtual docking-based screening approach, three benzene sulphonate compounds (named 1, 5 and 6) were identified as potential Loxosceles SMase D inhibitors. All compounds inhibited the hydrolysis of the sphingomyelin substrate by both recombinant and native SMases D. Compounds 5 and 6 acted as SMases D uncompetitive inhibitors with Ki values of 0.49 µM and 0.59 µM, respectively. Compound 1 is a mixed type inhibitor, and presented a Ki value of 0.54 µM. In addition, the three compounds inhibited the binding of SMases D to human erythrocytes and the removal of glycophorin C from the cell surface, which are important events in the complement-dependent haemolysis induced by Loxosceles venom. Moreover, compounds 5 and 6 reduced the binding of SMases to human keratinocytes membrane and the venom induced cell death. Importantly, compounds 5 and 6 also controlled the development of the necrotic lesion in an in vivo model of loxoscelism. Together, our findings indicate that the novel SMase D inhibitors presented here are able to suppress both local and systemic reactions induced by Loxosceles venoms. Since the number of Loxosceles envenomation accidents is currently growing worldwide, our results indicate that both inhibitors are promising scaffolds for the rational design of new drugs targeting SMases D from these spiders.

Trachelas tranquillus envenomation with presumed bacterial superinfection in a child.

A 27-month-old girl with a history of congenital myopathy presented with two indurated, pink plaques involving the right arm and left thigh. Closer examination identified central puncta within these plaques, which reportedly occurred at sites of witnessed arachnid bites. After confirmation of the spider species as Trachelas tranquillus, she was treated to address cutaneous inflammation and suspected superinfection using oral and topical antibiotics as well as topical corticosteroid resulting in prompt resolution of her lesions. Trachelas tranquillus should be considered as a possible source of inflammatory spider bites that can become superinfected.

Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D.

Loxoscelism refers to the clinical symptoms that develop after brown spider bites. Brown spider venoms contain several phospholipase-D isoforms, which are the main toxins responsible for both the cutaneous and systemic effects of loxoscelism. Understanding of the phospholipase-D catalytic mechanism is crucial for the development of specific treatment that could reverse the toxic effects caused by the spider bite. Based on enzymatic, biological, structural, and thermodynamic tests, we show some features suitable for designing drugs against loxoscelism. Firstly, through molecular docking and molecular dynamics predictions, we found three different molecules (Suramin, Vu0155056, and Vu0359595) that were able to bind the enzyme's catalytic site and interact with catalytically important residues (His12 or His47) and with the Mg2+ co-factor. The binding promoted a decrease in the recombinant brown spider venom phospholipase-D (LiRecDT1) enzymatic activity. Furthermore, the presence of the inhibitors reduced the hemolytic, dermonecrotic, and inflammatory activities of the venom toxin in biological assays. Altogether, these results indicate the mode of action of three different LiRecDT1 inhibitors, which were able to prevent the venom toxic effects. This strengthen the idea of the importance of designing a specific drug to treat the serious clinical symptoms caused by the brown spider bite, a public health problem in several parts of the world, and until now without specific treatment. J. Cell. Biochem. 118: 726-738, 2017. © 2016 Wiley Periodicals, Inc.

The black widow spider bite: differential diagnosis, clinical manifestations, and treatment options.

Unrecognized and untreated black widow spider bites cause significant pain, impairment, and rarely death. The widow venom, a powerful neurotoxin known as a-latrotoxin, causes muscle pain, diaphoresis, tachycardia, flushing, and hypertension. Treatment is usually symptomatic with a combination of opioid analgesics and muscle relaxants. If symptom resolution fails, an equine IgG antiserum is available, but a high index of clinical suspicion coupled with a knowledgeable patient history often allows successful treatment, especially when the treating physician possesses awareness of this type of bite and its usual course and possible complications.

Assessing and managing spider and scorpion envenomation.

Envenomation by spiders or scorpions is a public health problem in many parts of the world and is not isolated to the tropics and subtropics. Spiders and scorpions can be unintentionally transported globally, and keeping them as pets is becoming more popular, so envenomation can occur anywhere. Emergency nurses should be prepared to assess and treat patients who present with a bite or sting. This article gives an overview of the signs, symptoms and treatment of envenomation by species of arachnids that are clinically significant to humans.

[LOXOCELES BITE WOUND TREATMENT WITH SYNTHETIC POLYMER MATRIX]. / Herida por picadura de loxosceles tratada con una matriz sintética de polímeros nueva perspectiva en la cura avanzada de heridas complejas.

Loxocelism is a toxic condition produces by the venom inoculated by the bit of the recluse spider (genus Loxosceles). In can appear in two clinical forms: cutaneous loxocelism and viscerocutaneous Ioxocelim. The species Loxoceles rufescens, found in Spain, is responsible of cases of cutaneous loxocelism. Cutaneous loxocelism starts with an itch, later giving rise to intense pain, and it later takes either a more or less severe necrotic form or an edematous form. The latter, with a better prognosis, is the one we focus on here. The diagnosis is clinical. The systemic treatment consists in analgesics, antihistamines, corticosteroids, broad-spectrum antibiotics, and dapsone in severe cases. The local treatment is based on the cleaning and debridement of the wound, and in advanced treatments for complex wounds. It is not uncommon that such wounds require skin grafting. We present the case of an 18-year female bitten by a loxosceles on the dorsal area of the foot. She developed a deep tissue necrosis in the area. She presented systemic complications such as leucocitosis, fever, local infection and cellulitis. Systemic treatment and hospitalization were required, as well as advanced therapeutic care. Finally, cutaneous integrity was restored after 84 days.

Randomized controlled trial of intravenous antivenom versus placebo for latrodectism: the second Redback Antivenom Evaluation (RAVE-II) study.

STUDY OBJECTIVE: Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia. METHODS: In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions. RESULTS: Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom. CONCLUSION: The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.

First report of in vitro selection of RNA aptamers targeted to recombinant Loxosceles laeta spider toxins.

BACKGROUND: Loxoscelism is the envenomation caused by the bite of Loxosceles spp. spiders. It entails severe necrotizing skin lesions, sometimes accompanied by systemic reactions and even death. There are no diagnostic means and treatment is mostly palliative. The main toxin, found in several isoforms in the venom, is sphingomyelinase D (SMD), a phospholipase that has been used to generate antibodies intended for medical applications. Nucleic acid aptamers are a promising alternative to antibodies. Aptamers may be isolated from a combinatorial mixture of oligonucleotides by iterative selection of those that bind to the target. In this work, two Loxosceles laeta SMD isoforms, Ll1 and Ll2, were produced in bacteria and used as targets with the aim of identifying RNA aptamers that inhibit sphingomyelinase activity. RESULTS: Six RNA aptamers capable of eliciting partial but statistically significant inhibitions of the sphingomyelinase activity of recombinant SMD-Ll1 and SMD-Ll2 were obtained: four aptamers exert ~17% inhibition of SMD-Ll1, while two aptamers result in ~25% inhibition of SMD-Ll2 and ~18% cross inhibition of SMD-Ll1. CONCLUSIONS: This work is the first attempt to obtain aptamers with therapeutic and diagnostic potential for loxoscelism and provides an initial platform to undertake the development of novel anti Loxosceles venom agents.

Priapism after western black widow spider (Latrodectus hesperus) envenomation.

Priapism in children after a black widow spider bite is a rare phenomenon with only a few case reports noted in the literature. Black widow bites are commonly associated with pain, muscle cramping, hypertension, and tachycardia. Initial treatment includes pain control with opiate or opioid medications and benzodiazepines, with antivenom reserved for severe cases of envenomation manifested by uncontrolled pain or hypertension. Treatment with antivenom for priapism is not well described; however, it has been noted to resolve priapism in the few cases that have been reported. We present a case of a 3-year-old boy who was bitten by a black widow and presented with abdominal cramping and priapism.

Utilization of dapsone and hemoglobin in the epithelial skin regeneration therapy of cutaneous loxoscelism: A case report and integrative literature review.

BACKGROUND: Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their severity and location, cutaneous forms are managed with local cold application and systemic administration of antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics. OBJECTIVE: This study aimed to report a case of cutaneous loxoscelism and to identify the main dermatological manifestations associated with the Loxosceles spp bite. DESIGN AND SETTING: This case report and literature review was conducted in a Mexican university. METHODS: A detailed report on the medical management of a patient with cutaneous loxoscelism treated at the emergency department of a public hospital was published. Scopus, PubMed, Web of Science, and Google Scholar databases were searched to identify articles reporting cutaneous loxoscelism. The following keywords were used during the database search: "loxoscelism" OR "spider bite," OR "loxosceles" OR "loxosceles species" OR "loxosceles venom" OR "loxoscelism case report" AND "cutaneous" OR "dermonecrotic arachnidism." RESULTS: A 62-year-old female patient with cutaneous loxoscelism was treated with systemic dapsone and local heparin spray. Eighteen studies with 22 clinical cases were included in this systematic review. Of the 22 patients, 12 (54.5%) were men. L. rufescens was the predominant spider species. CONCLUSIONS: The administration of dapsone and heparin for the management of cutaneous loxoscelism demonstrated success in this case, with no sequelae observed. In general, the literature review indicated favorable outcomes in patients treated with antimicrobials and corticosteroids, with continuous healing of skin lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42023422424 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023422424).

It's Not a Spider Bite-It's MRSA!

Although there is an increased awareness of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), there remains a bias of the public and health-care workers to blame spiders as a cause of skin and soft tissue infection when there is no valid incriminated evidence for this assumption. MRSA is a formidable infection and remains a threat to human health. Recognition and proper treatment by practitioners remain of utmost importance to improve patient outcomes.

Envenomation by the Indian ornamental tarantula (Poecilotheria regalis): A case report on treatment with Latrodectus mactans antivenom.

Poecilotheria spiders are considered theraphosids of underestimated clinical importance, with bites from these species inducing symptoms such as severe pain and intense muscle cramps. However, there is no specific treatment for the envenomation caused by these species, which, while native to India and Sri Lanka, are widely distributed worldwide. The present study reports the case of a 31-year-old man bitten by a Poecilotheria regalis specimen. The patient's clinical presentation was similar to Latrodectus envenomation, and patient was treated with an L. mactans antivenom. Most of patient's symptoms improved (fasciculations, pain, erythema, and local swelling), except muscle cramps. A toxicological study conducted on mice did not show that L. mactans antivenom has a neutralizing effect on the toxicity of P. regalis. The present report discusses the envenoming process of Poecilotheria species and the possible neutralizing effect exerted by L. mactans antivenom.

Hypersensitivity vs. uncommonly severe local envenoming by the red-back spider, Latrodectus hasselti Thorell, 1870 (Araneae: Theridiidae).

The genus Latrodectus (Araneae: Theridiidae) consists of 35 widow spider species with global distribution. Envenoming by medically important species, latrodectism, commonly features bite site erythema and diaphoresis, variably severe pain that may be persistent, myalgia/cramping and/or myoclonus, autonomic symptoms, abdominal distress; severe envenoming can be prolonged and include serious effects such as oliguria, hypertension and, rarely, myocarditis/myocardial injury. Red-back spiders (Latrodectus hasselti) are the most common cause of envenoming in Australia and can cause the spectrum of effects noted for other medically important widow spiders. A 34-yr-old woman with a history of previous L. hasselti envenoming and treatment with antivenom was envenomed in her left ankle by a verified L. hasselti (hiding in her boot) while attending an appointment with her primary care physician. She reported some of the common effects of latrodectism including severe, prolonged pain, bite site diaphoresis, and malaise; however, she also developed marked edema that involved the entire left foot. She also exhibited mild hypertension and autonomic/non-specific effects limited to nausea, headache, and anxiety. She was effectively treated with red-back spider antivenom (a total of 4 ampoules) and supportive care; full resolution of the edema required almost 5 days. The uncommon clinical evolution of L. hasselti local envenoming observed in this patient may have been caused by a mixed picture of venom-induced effects and Type I hypersensitivity, but alternatively could be a rare, solely venom-induced manifestation. While provision of patient-centred care for anyone envenomed by Latrodectus spp. requires careful history collection and assessment of comorbidities, differentiation of atopic and direct venom effects may be challenging in some envenomed patients with established complex allergy history.

A randomized, double-blind, placebo-controlled trial of a highly purified equine F(ab)2 antibody black widow spider antivenom.

STUDY OBJECTIVE: Black widow spider antivenom has never been tested in a randomized clinical trial, to our knowledge. We explore various efficacy measures for a novel F(ab)2 antivenom in patients with moderate to severe pain caused by black widow spider envenomation. METHODS: A randomized, placebo-controlled, double-blind, clinical trial was conducted in 12 academic emergency departments. We included patients at least 10 years old with moderate to severe latrodectism. Subjects received either a single intravenous infusion of antivenom or placebo. Pain was assessed with the visual analog scale. The primary efficacy outcome was the difference in pre- and posttreatment visual analog scale score. Prospectively defined secondary outcomes included treatment failures and time to clinically important decrease in pain. RESULTS: Twenty-four subjects were enrolled between October 2005 and October 2006; 13 were randomized to antivenom and 11 to placebo. The median change in visual analog scale at 150 minutes posttreatment was -50.0 mm (Interquartile Range [IQR] -67, -41 mm) in the antivenom treatment group and -46.0 mm (IQR -51, 0 mm) in the placebo treatment group (P=.14). There were 7 treatment failures (64%; 95% confidence interval 35% to 92%) in the placebo group and 3 (23%; 95% confidence interval 0.2% to 46%) in the antivenom group (P=.06). The median time to a clinically important decrease in pain after treatment was shorter in the antivenom group compared with the placebo group (30 minutes [IQR 30, 60 minutes] versus 90 minutes [IQR 30, 90 minutes]; P=.03). No serious adverse events or deaths were reported. CONCLUSION: Although the overall reduction in pain was similar for antivenom- and placebo-treated subjects, antivenom reduced pain more rapidly than placebo. No significant adverse events occurred in either group.

Evolution in the choice of therapies used to treat latrodectism: Redback spider antivenom or standard analgesic medications. Nothing to rave about.

OBJECTIVES: Redback spider (RBS) antivenom (RBSAV) use appears to have decreased since the results of the RAVE-2 antivenom efficacy study were released. The aims of this study were to assess change in RBSAV use over time and compare responses to treatment for antivenom and other analgesics. METHODS: Retrospective audit of RBS bite referrals to a toxicology unit, from January 2010 to January 2022. Data included demographics, pain severity, treatment (analgesia or RBSAV), response to treatment, re-presentation rate, adverse events, change in antivenom use over time. RESULTS: Of 270 presentations, 157 with moderate or severe pain were included (RBSAV n = 51, analgesia n = 106). Median age was 39 years, n = 81 (51%) female. Those receiving antivenom were more likely to report severe pain n = 46/51 (84%) versus n = 68/106 (58%) (P = 0.006). Eighty-three percent of antivenom doses were administered between 2010 and 2013. Analgesia-only group received various combinations of paracetamol, NSAIDs, and opioids. In those receiving RBSAV, 17/48 (35%), 26/48 (54%), 5/48 (10%) reported a partial, complete or no reduction in pain, respectively, versus 30/77 (39%), 43/77 (58%) and 4/77 (5%), for analgesia-only group. Post-treatment pain was not recorded in three RBSAV and 28 analgesia-only patients. Pain reduction was no different for intravenous and intramuscular antivenom. Re-presentation for ongoing pain was more common in the analgesia-only group, 16/106 (15%) versus 1/51 (2%) for antivenom (P = 0.013). CONCLUSION: Antivenom use fell over the study period. There was no difference in pain relief between RBSAV and analgesia-only groups. RBSAV, regardless of route of administration, was no better than standard analgesics in pain reduction in the present study.

Anaphylaxis to black widow spider antivenom.

Black widow spider envenomation is commonly reported to poison centers. Black widow spider envenomation produces a clinical syndrome, known as latrodectism, characterized by headache, nausea, vomiting, several muscle cramping and pain, joint stiffness, hypertension, and regional diaphoresis. Black widow spider antivenom (Merck & Co, Inc, West Point, PA USA) is an effective and relatively safe treatment option. There is 1 clear case of anaphylaxis secondary to black widow spider antivenom reported in the medical literature. Here, we report a case of anaphylaxis to antivenom. A 12-year-old boy presented to the emergency department (ED) with diffuse, severe pain 2 1/2 hours after being bitten by a black widow spider on the right lower extremity. In the ED, the patient failed analgesic therapy with fentanyl and was given black widow spider antivenom. Within 45 minutes, he exhibited signs and symptoms consistent with anaphylaxis, including wheezing, chest tightness, pruritus, and urticarial rash. The patient was given standard therapy for anaphylaxis, and all of his signs and symptoms (including the pain secondary to the black widow envenomation) resolved over 6 hours of observation. Leading experts agree that the use of antivenom is indicated in cases of severe envenomation not responsive to standard therapy. Despite concern that the antivenom is an equine-derived whole IgG and can precipitate early hypersensitivity reactions, there is only 1 other reported case of anaphylaxis to the antivenom in the medical literature.