The use of therapeutic plasma exchange in systemic loxoscelism induced treatment resistant hemolytic anemia: A case report.

Brown recluse spider bites can lead to severe reactions such as skin necrosis,hemolytic anemia, and multiorgan failure, which can be life-threatening. Therapeutic plasma exchange has been reported to provide clinical benefit for such cases. In thisreport, we present a case of a brown recluse spider bite that was successfully treated with therapeutic plasma exchange and compare it with previous case reports.

Role of the complement system in kidney cell death induced by Loxosceles venom Sphingomyelinases D.

Envenomation by Loxosceles spiders can result in local and systemic pathologies. Systemic loxoscelism, which can lead to death, is characterized by intravascular hemolysis, platelet aggregation, and acute kidney injury. Sphingomyelinase D (SMase D) in Loxosceles spider venom is responsible for both local and systemic pathologies, and has been shown to induce metalloprotease activity. As the complement system is involved in many renal pathologies and is involved in hemolysis in systemic loxoscelism, the aim of this study was to investigate its role and the role of complement regulators and metalloproteases in an in vitro model of Loxosceles venom induced renal pathology. We investigated the effects of the venom/SMase D and the complement system on the HK-2 kidney cell line. Using cell viability assays, western blotting, and flow cytometry, we show that human serum, as a source of complement, enhanced the venom/SMase D induced cell death and the deposition of complement components and properdin. Inhibitors for ADAM-10 and ADAM-17 prevented the venom induced release of the of the complement regulator MCP/CD46 and reduced the venom/SMase D induced cell death. Our results show that the complement system can contribute to Loxosceles venom induced renal pathology. We therefore suggest that patients experiencing systemic loxoscelism may benefit from treatment with metalloproteinase inhibitors and complement inhibitors, but this proposition should be further analyzed in future pre-clinical and clinical assays.

A brown recluse spider bite wound: a case report and literature review.

DECLARATION OF INTEREST: The authors have no conflicts of interest.

Role of ErbB and IL-1 signaling pathways in the dermonecrotic lesion induced by Loxosceles sphingomyelinases D.

Sphingomyelinase D (SMase D), the main toxic component of Loxosceles venom, has a well-documented role on dermonecrotic lesion triggered by envenomation with these species; however, the intracellular mechanisms involved in this event are still poorly known. Through differential transcriptomics of human keratinocytes treated with L. laeta or L. intermedia SMases D, we identified 323 DEGs, common to both treatments, as well as upregulation of molecules involved in the IL-1 and ErbB signaling. Since these pathways are related to inflammation and wound healing, respectively, we investigated the relative expression of some molecules related to these pathways by RT-qPCR and observed different expression profiles over time. Although, after 24 h of treatment, both SMases D induced similar modulation of these pathways in keratinocytes, L. intermedia SMase D induced earlier modulation compared to L. laeta SMase D treatment. Positive expression correlations of the molecules involved in the IL-1 signaling were also observed after SMases D treatment, confirming their inflammatory action. In addition, we detected higher relative expression of the inhibitor of the ErbB signaling pathway, ERRFI1, and positive correlations between this molecule and pro-inflammatory mediators after SMases D treatment. Thus, herein, we describe the cell pathways related to the exacerbation of inflammation and to the failure of the wound healing, highlighting the contribution of the IL-1 signaling pathway and the ERRFI1 for the development of cutaneous loxoscelism.

Spider bites in France: Epidaemiology of cases occurring in 10 years in metropolitan France.

Spiders are often wrongly designated as responsible for cutaneous eruptions. We aim to describe spider bites and the spider species implicated in metropolitan France. A retrospective observational study was conducted for all reported cases of spider bites from 2007 to 2018 extracted from the French Poison Control Centers (PCCs) information system, after exclusion of non-native spiders. We described identification of the spider, level of certainty of the bite, symptoms and severity of cases. 1194 cases of spider bites met the inclusion criteria. The average age of the patients was 36.9 ± 19.8 years. Identification of the species or at least that a spider was implicated was only possible in 346 cases (29.0%). Loxosceles were involved in 53 cases (4.4%), Latrodectus in 46 cases (3.9%) and Cheiracanthium in 35 cases (2.9%). In one third of cases, the involved spider was not known to be present where the bite occurred. Where most of the patients (n = 1111, 93%) reported at least one cutaneous symptom, most of the symptoms were neurological. The bite was considered proven in only 242 cases (20%). Despite the efforts of arachnologists to educate the public, the fear of spiders is still alive in France, where spider bite is rare with low severity and often unproven.

Cutaneous mammary loxoscelism: An unknown cause of breast inflammation: A case report and review of the literature.

Envenomation due to a Loxosceles spider bite is a rare event in France and no case concerning the breast has yet been reported. We report the case of a 48-year-old woman who presented at Saint-Etienne University Hospital with a pulsatile pain in her left breast two days after feeling a fleeting bite. An abscess was diagnosed and antibiotics were prescribed. A few days later, a necrotic zone appeared around the areola and 75 percent of the surrounding skin was inflamed. The patient reported a persistent fever and a burning pain in her breast. Loxoscelism was finally concluded and surgical debridement was undertaken, followed by supervised wound therapy and local skin care. Complete healing was achieved after 4 weeks of treatment. The diagnosis of loxoscelism is generally presumptive, as the bite is usually painless and the spider rarely captured. Its diagnosis should be considered when an abscess responds poorly to antibiotics.

Clinical aspects, diagnosis and management of Loxosceles spider envenomation: literature and case review.

The genus Loxosceles comprises 140 species widely distributed around the world. These spiders are nocturnal, sedentary and remarkably nonaggressive, although they cause accidents in humans with wide degrees of severity, generating signs and symptoms that define the clinical condition known as loxoscelism. Its local signs and symptoms were first reported in 1872, and over the years, a large medical literature has been accumulated; unfortunately, it is not always trustworthy. Assessing the reliability of such information, we reviewed 120 case reports of loxoscelism published in 84 articles over the past 20 years. This search allowed us to gather information on the clinical aspects, diagnosis and treatment of loxoscelism, showing that the severity of these accidents has multiple degrees and that it is influenced by many factors. Thus, coupled with epidemiological and species occurrence information, this study can be a useful tool for the clinical practice of loxoscelism. It may support and provide a multidisciplinary view that should be taken into consideration when establishing the therapeutic approach in cases of Loxosceles envenomation.

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.

Infection Due to Saksenaea vasiformis Following a Spider Bite.

Cutaneous mucormycosis due to Saksenaea vasiformis species is exceptional. There have been about 40 reported cases worldwide, with most being fatal. We report an exceptional nonlethal case of mucormycosis due to S. vasiformis following a spider bite. The patient was in an immunosuppressed state owing to previous chemotherapy and diabetes mellitus. The origin of the inoculation was the bite of a Loxosceles laeta spider, which caused loxoscelism. The initial skin injury was quickly progressive, requiring amputation of the right upper limb. After surgical intervention and suitable antifungal treatment, the patient was discharged with resolution of accompanying pulmonary disease. Infections due to S. vasiformis are probably underdiagnosed. To avoid fatal outcomes, a high index of clinical suspicion in patients with quickly progressive necrotic lesions of soft tissues and systemic dissemination is important.

Autologous fibroblasts for the treatment of cutaneous loxoscelism: First experience.

Several treatments have been described for cutaneous loxoscelism (CL), but the quality of available evidence is insufficient for the elaboration of a therapeutic consensus. Dapsone has shown beneficial effects on stopping the inflammatory phenomenon and accelerating the recovery. It is recommended to start dapsone once the visceral involvement is ruled out if glucose-6-phosphate dehydrogenase levels are normal. Autologous fibroblast (AF) therapy is a novel therapy that has been successfully used in bioengineering as skin substitutes for surgical wounds and burns, diabetic and pressure ulcers, and other aesthetic purposes. Interestingly, there are no reports of AFs in CL. We present a case of CL in which the necrotic process was stabilised with dapsone, but the healing of the ulcer was not achieved. Three weekly applications of AFs 100 000/cm2 were performed on a biocompatible polymer matrix, with optimal response within 2 months. This represents the first report of AFs in CL, setting the stage for future studies.

Matching global and regional distribution models of the recluse spider Loxosceles rufescens: to what extent do these reflect niche conservatism?

The Mediterranean recluse spider, Loxosceles rufescens (Dufour, 1820) (Araneae: Sicariidae) is a cosmopolitan spider that has been introduced in many parts of the world. Its bite can be dangerous to humans. However, the potential distribution of this alien species, which is able to spread fairly quickly with human aid, is completely unknown. Using a combination of global and regional niche models, it is possible to analyse the spread of this species in relation to environmental conditions. This analysis found that the successful spreading of this species varies according to the region invaded. The majority of populations in Asia are stable and show niche conservatism, whereas in North America this spider is expected to be less successful in occupying niches that differ from those in its native region and that do not support its synanthropic way of living.

Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders.

Venoms of the sicariid spiders contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These enzymes convert sphingolipid and lysolipid substrates to cyclic phosphates by activating a hydroxyl nucleophile present in both classes of lipid. The most medically relevant substrates are thought to be sphingomyelin and/or lysophosphatidylcholine. To better understand the substrate preference of these toxins, we used (31)P NMR to compare the activity of three related but phylogenetically diverse sicariid toxins against a diverse panel of sphingolipid and lysolipid substrates. Two of the three showed significantly faster turnover of sphingolipids over lysolipids, and all three showed a strong preference for positively charged (choline and/or ethanolamine) over neutral (glycerol and serine) headgroups. Strikingly, however, the enzymes vary widely in their preference for choline, the headgroup of both sphingomyelin and lysophosphatidylcholine, versus ethanolamine. An enzyme from Sicarius terrosus showed a strong preference for ethanolamine over choline, whereas two paralogous enzymes from Loxosceles arizonica either preferred choline or showed no significant preference. Intrigued by the novel substrate preference of the Sicarius enzyme, we solved its crystal structure at 2.1 Å resolution. The evolution of variable substrate specificity may help explain the reduced dermonecrotic potential of some natural toxin variants, because mammalian sphingolipids use primarily choline as a positively charged headgroup; it may also be relevant for sicariid predatory behavior, because ethanolamine-containing sphingolipids are common in insect prey.

Documented cutaneous loxoscelism in the south of France: an unrecognized condition causing delay in diagnosis.

BACKGROUND: Loxoscelism is an envenomation due to a bite by spiders of the genus Loxosceles, very well known on the American continent but unrecognized in Europe. CASE REPORT: We report the case of a 36-year-old woman, without any medical history or treatment, who went to a University Hospital in the South of France, for a painful skin lesion on the internal part of her left thigh, which appeared in the morning and developed rapidly during the day. She was directed to the infectious disease department with a diagnosis of skin infection. In spite of the antibiotics, the lesion increased, with a hemorrhagic central blister, an irregular ecchymotic center, a pale perimeter, and an extensive inflammatory and indurate oedema affecting the whole thigh. There was also a low-grade fever, chills, intense pain and a generalized scarlatiniform exanthema. The lesion was finally diagnosed as cutaneous loxoscelism, then confirmed by collection and identification of a Loxosceles rufescens spider killed by the patient the morning of the occurrence of the lesion. Following an initial symptomatic treatment, the development of a necrotic ulcer justified a delayed surgical reconstruction, after stabilization of the lesion. CONCLUSIONS: Loxosceles bites are usually painless and rarely noticed by patients, often leading to a presumptive diagnosis. Therefore, in the case of a dermonecrotic lesion developing unfavourably with antibiotics, cutaneous loxoscelism should be one of the diagnoses to be considered.

Niche modelling of the Chilean recluse spider Loxosceles laeta and araneophagic spitting spider Scytodes globula and risk for loxoscelism in Chile.

In Chile, all necrotic arachnidism is attributed to the Chilean recluse spider Loxosceles laeta (Nicolet) (Araneae: Sicariidae). It is predated by the spitting spider Scytodes globula (Nicolet) (Araneae: Scytodidae). The biology of each of these species is not well known and it is important to clarify their distributions. The aims of this study are to elucidate the variables involved in the niches of both species based on environmental and human footprint variables, and to construct geographic maps that will be useful in estimating potential distributions and in defining a map of estimated risk for loxoscelism in Chile. Loxosceles laeta was found to be associated with high temperatures and low rates of precipitation, whereas although S. globula was also associated with high temperatures, its distribution was associated with a higher level of precipitation. The main variable associated with the distribution of L. laeta was the human footprint (48.6%), which suggests that this is a highly invasive species. Similarly to other species, the distribution of L. laeta reaches its southern limit at the Los Lagos region in Chile, which coincides with high levels of precipitation and low temperatures. The potential distribution of L. laeta in Chile corresponds to the distribution of cases of loxoscelism.

Interactions Between the Chilean Recluse Spider (Araneae: Sicariidae) and an Araneophagic Spitting Spider (Araneae: Scytodidae).

In Chile, all necrotic arachnidism is attributed to the Chilean recluse spider, Loxosceles laeta Nicolet, a species that shares the microenvironmental habitats with the spitting spider Scytodes globula Nicolet. The latter species has been proposed as a potential predator of L. laeta. For this research, we studied the interaction between both species during individual encounters to assess the possibility of population regulation of L. laeta cohorts exposed to this potential predator. We found that in most encounters S. globula prevailed. Also, S. globula preys on spiderlings of L. laeta, with a population effect on cohorts of this species. These findings suggest that S. globula may be influencing L. laeta populations in central Chile. The population regulation of L. laeta by predation would be important because this species, in the absence of predators, has a high reproductive rate, and it can maintain populations of large size. However according to our results, although S. globula may aid in the reduction of both spiderling and adult L. laeta populations, and perhaps other Loxosceles species, it is insufficient for biological control of Loxosceles species. Its presence together with other control measures such as hygiene of the rooms can help to decrease loxoscelism incidence.

Immune-mediated mechanism for thrombocytopenia after Loxosceles spider bite.

Loxoscelism, characterized by high fever, vomiting, malaise, a dermonecrotic lesion, and thrombocytopenia, was diagnosed in a 3-year-old female. Clinical laboratory and dermatological signs are described. Blood test showed a transient hypercoagulable state and the presence of IgG antibodies against platelets, suggesting an immune-mediated mechanism for platelet destruction, in addition to the direct toxic effect of the spider venom. The finding of platelet antibodies after a Loxosceles spider bite has not been previously reported.

Protective effects of mesenchymal stromal cell-derived secretome on dermonecrosis induced in rabbits by Loxosceles intermedia spider venom.

Background: Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the Loxosceles genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by Loxosceles intermedia spider venom in rabbits. Methods: Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 µg of L. intermedia venom, diluted in 100 µL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 µg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 µg of secretome, via ID and Group 4 (G4), received 60 µg of secretome by intravenous route. Rabbits were evaluated daily and after 15 days were euthanized, necropsied and skin samples around the necrotic lesions were collected for histological analysis. Results: Rabbits of G1 did not present edema, erythema, hemorrhagic halo, or necrosis. In animals from G2, G3, and G4, edema appeared after 6h. However, minor edema was observed in the animals of G2 and G3. Hemorrhagic halo was observed in animals, six hours and three days after, on G2, G3, and G4. Macroscopically, in G4, only one animal out of four had a lesion that evolved into a dermonecrotic wound. No changes were observed in the skin of the animals of G1, by microscopic evaluation. All animals challenged with L. intermedia venom showed similar alterations, such as necrosis and heterophilic infiltration. However, animals from G4 showed fibroblast activation, early development of connective tissue, neovascularization, and tissue re-epithelialization, indicating a more prominent healing process. Conclusion: These results suggest that secretome from mesenchymal stromal cells cultured in a xeno-free and human component-free culture media can be promising to treat dermonecrosis caused after Loxosceles spiders bite envenoming.

Comparative medical importance of spider bites in Spain over 1997-2020: a retrospective study based on hospital cases coded using ICD.

Envenomation by terrestrial toxic animals is considered a serious risk to human health worldwide. Snakes, hymenopterans, spiders, and scorpions have mainly attracted the attention of medical literature. However, the relative importance of spiders has been studied only in a few countries. Here, we present the first retrospective study on the incidence of spider bites requiring hospital care in Spain, compared to bites or stings from snakes, hymenopterans, and scorpions. Using ICD9MC and ICD10 databases from the World Health Organization's International Classification of Diseases for the period 1997-2020, we quantified the cases of envenomation by spiders, compared to those by other terrestrial toxic animals, the demographic data of envenomation cases, the relative severity of spider bites, and the geographic distribution of envenomation cases. Overall, the incidence of acute intoxication by terrestrial toxic animals in Spain was ca. 1.23 cases per million inhabitants. In decreasing order of importance, cases were due to snakes, hymenopterans, spiders, scorpions, and myriapods. Fatal cases were extremely rare, caused mainly by hymenopterans. No fatalities were caused by spiders, scorpions, and myriapods. A greater incidence of snake bites occurred in northern Spain, but no geographical trends were found for spider bites or scorpion stings. Severe poisoning or life-threatening cases due to bites or stings from toxic terrestrial animals in Spain seems to be very low, especially for spiders, compared to other countries in the world. In general, spiders do not present a risk to human health and should not be considered a major driver of morbidity.

Integrative taxonomy reveals first record of Loxoscelesrufescens (Dufour, 1820) (Araneae, Sicariidae) in the Philippines.

Background: The spider family Sicariidae Keyserling, 1880 represented by the synanthropic Mediterranean recluse spider, Loxoscelesrufescens (Dufour, 1820), is reported in the Philippines for the first time, based on morphological and molecular data. The introduced spider was observed in a small cave (Kamantigue Cave) in Lobo, Batangas Province. Considering the medical importance of this spider, the proximity of its habitat to human habitation and tourist sites poses a potential public health concern. New information: This study reports on the first record of the family Sicariidae in the Philippines and the fourth recorded occurrence of L.rufescens in Southeast Asia.

Fatal Viscerocutaneous Brown Recluse Envenomation With Orbital Compartment Syndrome.

Loxosceles is an arachnid genus comprising several species in the United States, popularly known as brown recluse spiders. The venom is cytotoxic, complex, and has a mixture of many proteins, some of which function as proteases. Envenomation can cause necrotic skin lesions that may become extensive and take many months to heal. Even more rarely, venom may cause systemic effects, leading to widespread hemolysis, coagulopathy, and death. These symptoms typically occur rapidly within 24-48 hours following the bite. We describe a rare case of a 44-year-old male with fatal systemic loxoscelism with orbital compartment syndrome requiring emergent lateral canthotomy and cantholysis.