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To ascertain whether a dose response exists between the dose of brown recluse spider venom (BRSV) and the cutaneous and coagulation effects in a rabbit model. Cutaneous necrosis is a serious complication of brown recluse spider envenomation (spider bite with venom). Disseminated intravascular coagulation (DIC) is a dreaded complication of brown rec...
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Context 1
... lesions in the rabbits caused by the experimental whole venom and sphingomyelinase injections were characterized by more hemorrhage and less cutaneous necrosis than is seen in humans. A typical 24-hour post inoculation lesion in rabbits is shown in Figure 1. The assay results showed that the cotton swabs allowed for more detectable venom recovery than were obtained from the Dacron swabs (Figures 2 and 3). ...
Similar publications
Loxosceles reclusa (L.reclusa) is known to bite humans, and its venom includes several enzymes that cause clinical symptoms. Loxoscelism, a condition due to being bitten by Loxosceles spiders, commonly known as recluses, can involve a range of clinical conditions, from local cutaneous lesions to severe systemic involvement. The diagnosis of loxosce...
Citations
... The components of Loxosceles spider venom include various proteins and peptide toxins. However, phospholipase D or sphingomyelinase D toxin is the major cause of skin necrosis and hemolysis in patients with loxoscelism [1,2,23,24]. Several factors have been associated with the progression of skin necrosis, such as the amount of venom inoculated, the crushing of the spider at the time of the bite, and the characteristics of the spider itself (species, sex, and ontogenetic stage) [1,2,7,23,24]. ...
... However, phospholipase D or sphingomyelinase D toxin is the major cause of skin necrosis and hemolysis in patients with loxoscelism [1,2,23,24]. Several factors have been associated with the progression of skin necrosis, such as the amount of venom inoculated, the crushing of the spider at the time of the bite, and the characteristics of the spider itself (species, sex, and ontogenetic stage) [1,2,7,23,24]. In the present manuscript, patients in clinical cases 2 and 3 presented with mild to moderate skin lesions. ...
Spiders are the most numerous arthropods of the arachnid class. More than 45 thousand species of spiders have been identified, and only a few are dangerous to humans. Among them, the “violin spider” or “brown spider” of the genus Loxosceles (family Sicariidae) has a worldwide distribution, and its bite can cause loxoscelism. Initial treatment of a Loxosceles spider bite includes application of local cold, rest, elevation of the extremity if possible, and systemic pharmacotherapy with antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics or nonsteroidal anti-inflammatory drugs. During cutaneous or systemic loxoscelism, administration of Loxosceles antivenom (immunoglobulin (Ig)G F(ab’)2 fragments) may be indicated to prevent progression to severe systemic phases. In this manuscript, we present three cases of patients with loxoscelism treated with the fabotherapeutic Reclusmyn®, developed and manufactured in Mexico. Two patients had a satisfactory outcome without severe skin or systemic damage. Only one patient with loxoscelism, despite early initiation of antivenom, had extensive skin lesions that healed satisfactorily, leaving only a non-disabling scar. Due to the global presence of this clinical problem, further studies are needed to establish local and general guidelines for the treatment and prevention of loxoscelism. This will allow health professionals to provide more efficient and higher quality medical care and feel supported in their decisions.
... A sphingomyelinase D-like from R. microplus was expressed in a bacterial system as a potential antigen target, but the enzymatic activity was not characterized (Castellanos-Mendoza et al., 2014). In a rabbit model, injection of brown spider venom resulted in coagulopathy with increased clotting time (McGlasson et al., 2007), and it was suggested that tick sphingomyelinase D may play an important role in the tick feeding process when combined with other saliva molecules (Rajendran et al., 2021). ...
Sphingomyelinase D is a toxin present in venomous spiders and bacteria and is associated with infection symptoms in patients affected by spider bites. It was observed that in Ixodes scapularis ticks, sphingomyelinase-like protein secreted in saliva can modulate the host immune response, affecting the transmission of flavivirus to the host via exosomes. In this work, a sphingomyelinase D-like protein (RmSMase) from R. microplus, a tick responsible for economic losses and a vector of pathogens for cattle, was investigated. The amino acid sequence revealed the lack of important residues for enzymatic activity, but the recombinant protein showed sphingomyelinase D activity. RmSMase shows Ca2+ and Mg2+ dependence in acidic pH, differing from IsSMase, which has Mg2+ dependence in neutral pH. Due to the difference between RmSMase and other SMases described, the data suggest that RmSMase belongs to SMase D class IIc. RmSMase mRNA transcription levels are upregulated during tick feeding, and the recombinant protein was recognized by host antibodies elicited after heavy tick infestation, indicating that RmSMase is present in tick saliva and may play a role in the tick feeding process.
... Thrombocytopenia, prolongation of prothrombin time, and activated partial thromboplastin time were found, as well as erythrocyte abnormalities in the blood smear and a decrease in CGMH in the VLoxo group (20). This allows us to establish the criteria to consider DIC. ...
Objectives:
Spiders of the Loxosceles genus, known as violin spiders, produce venom with dermonecrotic and systemic effects, as it is a species widely distributed in the world, its study represents a high medical relevance. Systemic loxoscelism, which occurs in 1 in 5 cases and is the most frequent in children, can be fatal, so the study of effective therapy is of great relevance. In the present study, we compared different therapeutic options to mitigate the systemic effects of Loxosceles boneti venom in a model in which prepubertal rats were used.
Materials and methods:
A model of systemic intoxication by L. boneti venom was provoked in male Wistar rats. Study groups were formed: healthy control, with venom and untreated control, treatment with N-acetylcysteine, and/or hyperbaric oxygenation therapy. Subsequently, pathological analysis of the kidney and lung was performed. The oxidant-antioxidant response was evaluated, and molecular analysis of the COX-1 and COX-2 enzymes was performed.
Results:
Regenerative changes were observed at the cellular level in both treatments, being more noticeable in the hyperbaric oxygen therapy (HBO) group. The anti-oxidant response was outstanding in the same group.
Conclusion:
Both treatments offer considerable benefits, however; further studies are needed to provide adequate therapeutics.
... The main component of the venom, a phospholipase D toxin, also known as a sphingomyelinase D toxin, is responsible for inducing the skin necrosis and hemolysis observed in some cases [8,9]. Experimental studies have shown that the evolution to skin necrosis in loxoscelism is associated with the amount of venom injected [10,11], as well as with the species, sex, and ontogenetic stage of the spider involved [12][13][14]. ...
... Sams et al. [25] reported that 11 (58%) of 19 patients diagnosed with loxoscelism evolved to necrosis, and Del Puerto et al. [26] reported that 10 (59%) of 17 such patients evolved to residual ulcer. In the present study, with the exception of the spider species, mostly identified as L. gaucho, it was not possible to assess any of the other factor that have been found to be associated with necrosis in previous experimental studies [10][11][12][13][14]. However, the time from bite to admission was longer among the patients who evolved to necrosis than among those who did not. ...
Background:
Spiders of the genus Loxosceles are distributed throughout tropical and temperate regions worldwide. Loxosceles spp. bites may evolve to necrosis, with or without intravascular hemolysis. There is no consensus regarding the best treatment to prevent necrosis. The objective of this study was to evaluate the factors associated with the development of necrosis and the impact that antivenom administration has on the evolution of cutaneous loxoscelism.
Methodology/principal findings:
This was a prospective observational study carried out at a referral center for envenoming. Over a 6-year period, we included 146 patients with a presumptive or definitive diagnosis of loxoscelism. Depending on the symptom severity, a polyvalent anti-arachnid antivenom was administered or not-in 74 cases (50.7%) and 72 cases (49.3%), respectively. Cutaneous and systemic manifestations were assessed at admission and weekly thereafter. Adverse reactions to the antivenom were also evaluated. Cutaneous loxoscelism was observed in 141 cases (96.6%), and the spider was identified in 29 (19.9%). The mean time from bite to antivenom administration was 41.6 ± 27.4 h. After discharge, 130 patients (90.9%) were treated with corticosteroids, antihistamines and analgesics being prescribed as needed. The probability of developing necrosis was significantly lower among the patients who were admitted earlier, as well as among those who received antivenom (p = 0.0245). Among the 74 patients receiving antivenom, early and delayed adverse reactions occurred in seven (9.5%) and four (5.4%), respectively. Local infection was observed only in three (2.3%) of the 128 patients for whom that information was available.
Conclusions/significance:
Necrosis after a Loxosceles sp. bite appears to more common when hospital admission is delayed or when antivenom is not administered. In addition, the administration of a polyvalent anti-arachnid antivenom appears to be safe, with a relatively low rate of adverse reactions.
... frequent, but more severe, called systemic or viscero-cutaneous loxoscelism (VCL). The clinical manifestations of loxoscelism (CL or VCL) depend on different factors, such as the amount and concentration of inoculated venom, the anatomical location of the bite, the susceptibility of the host, and the species and gender of the spider [7][8][9]. ...
Background
Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism.
Methods
The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot.
Results
We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider.
Conclusions
People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.
Electronic supplementary material
The online version of this article (10.1186/s40409-018-0155-x) contains supplementary material, which is available to authorized users.
... en 1987 en Perú 2 . Clínicamente puede presentarse en uno de los dos siguientes cuadros, el cutáneo-visceral (sistémico) y cutáneonecrótico (cutáneo) 3 . ...
... Mac Glasson y cols. 3 , usando modelos animales, en un experimento similar al de Tavares, estudió el efecto del veneno en la coagulación y en la piel. Recolectó y analizó muestras a las 24, 48 y 72 h. ...
... El cambio en el perfil de coagulación, está más relacionado al problema necrótico, donde las lesiones cutáneas presentan en su histopatología, presencia de vasculitis y trombosis 3,6 . En estos cambios, se observa una activación de la cascada de coagulación y agregación plaquetaria, lo que explica los cambios en el perfil, especialmente en el número de plaquetas. ...
... Alpha2-M by making a complex with protease inhibits the proteolytic activity (Nagaraju and Kemparaju 2011). In in vivo system venom produces cumulative effect of all toxins leading to diverse action, both locally and systemically (Mc Glasson et al. 2007). Metalloproteases play a major role in both local and systemic toxicity by degrading ECM molecules to decipher the integrity as well as the blood coagulation components inhibiting blood coagulation. ...
The Hippasa (funnel web) spiders exhibit varied geographical distribution, and the clinical manifestations following spider bites include hemorrhage followed by necrosis with gravitational spreading and occasional systemic manifestations. Hippasa spider venoms are complex mixture of toxins which includes metalloprotease, hyaluronidase, serine protease, neurotoxins, and other small molecular weight components. The mechanisms by which the toxins act and exert their pathological activities have been studied. The objective is to provide insights into the Hippasa spider venom components and its mechanism of action.
... Alpha2-M by making a complex with protease inhibits the proteolytic activity (Nagaraju and Kemparaju 2011). In in vivo system venom produces cumulative effect of all toxins leading to diverse action, both locally and systemically (Mc Glasson et al. 2007). Metalloproteases play a major role in both local and systemic toxicity by degrading ECM molecules to decipher the integrity as well as the blood coagulation components inhibiting blood coagulation. ...
The Hippasa (funnel web) spiders exhibit varied geographical distribution, and the clinical manifestations following spider bites include hemorrhage followed by necrosis with gravitational spreading and occasional systemic manifestations. Hippasa spider venoms are complex mixture of toxins which includes metalloprotease, hyaluronidase, serine protease, neurotoxins, and other small molecular weight components. The mechanisms by which the toxins act and exert their pathological activities have been studied. The objective is to provide insights into the Hippasa spider venom components and its mechanism of action.
... [8,9] Commonly reported manifestations are dermatologic, [10] hematologic, [11,12] nephrologic, [10] musculoskeletal [10] and neurologic [13]. Despite the research performed [14] and the Loxosceles-sensitive ELISA created [15], as of today the diagnosis remains clinical, based on history provided by the patient. The need for treatment is highlighted by the various modalities used so far including dapsone, glucocorticoids, hyperbaric oxygen and surgery. ...
A 63-year-old female with history of a resected frontal lobe meningioma presented with bilaterally decreased vision after a bite from a brown recluse spider. The exam was significant for a left relative afferent pupillary defect, bilateral optic nerve pallor, decreased foveal sensitivity in the left eye and new bilateral visual field defects, despite stability of her meningioma. The findings remained stable at 1-year follow-up. To our knowledge, this is the first reported case of optic neuropathy secondary to a brown recluse spider bite. Visual field tests performed prior to the bite allowed us to compare and localize changes related to the bite.
... Sphingomyelinase D, a key component of Loxosceles venom (Forrester et al., 1978) activates complement, endothelial and epithelial cells, as well as endogenous metalloproteinases (Patel et al., 1994;Gomez et al., 1999;Tambourgi et al., 2000;Veiga et al., 2001;Tambourgi et al., 2005;Paixão-Cavalcante et al., 2006;Tambourgi et al., 2007). Clinical manifestations evoked by Loxosceles envenomation vary depending on the amount of venom injected, anatomic location of the bite, and host susceptibility, as well as on spider species, sex and age (Futrell, 1992;Gonçalves de Andrade et al., 1999;de Oliveira et al., 2005;McGlasson et al., 2007). Classically, loxoscelism have been classified into two forms: cutaneous and cutaneous-hemolytic (also known as systemic or viscerocutaneous loxoscelism). ...
Loxosceles spiders are found globally, especially in South and North America. In Brazil, approximately 10,000 cases of Loxosceles spp. spider bites are reported annually. Herein we analyzed 81 patients diagnosed as either cutaneous or cutaneous-hemolytic loxoscelism, in a geographical area where most accidents are caused by Loxosceles gaucho, and we report their clinical and laboratory data obtained during week 1 and 2 after the bite. Massive hemolysis was noticed in only 2 cases, but high serum bilirubin and LDH levels, suggestive of hemolysis, were noticed in 25 cases on admission. Anemia was not frequent (14.7%), and reticulocytosis was particularly noticed during week 2 (in 56% of patients). High D-dimer levels were suggestive of endothelial cell activation and intravascular thrombin generation, but thrombocytopenia was noticed in only 17.6% of patients in week 1. Acute kidney injury (AKI) only occurred in patients with massive hemolysis. The definitive diagnosis of overt disseminated intravascular coagulation (DIC) could not be established on admission. Fever was associated with the presence of hemolysis (p = 0.03). Altogether, these findings provide evidence that mild hemolysis is frequent in loxoscelism and suggest that AKI is uncommon, exclusively occurring in patients with massive hemolysis.
