RESUMO
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).
Assuntos
Dapsona , Picada de Aranha , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Dapsona/uso terapêutico , Picada de Aranha/tratamento farmacológico , Hemoglobinas , Heparina , Corticosteroides , RegeneraçãoRESUMO
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.
Assuntos
Picada de Aranha , Venenos de Aranha , Aranhas , Animais , Humanos , Antivenenos/efeitos adversos , Hospitalização , Necrose , Picada de Aranha/tratamento farmacológico , Picada de Aranha/complicações , Picada de Aranha/diagnóstico , Venenos de Aranha/efeitos adversos , Estudos ProspectivosRESUMO
Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and loxoscelism. Present and future aspects of loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field.
Assuntos
Fosfolipase D/história , Diester Fosfórico Hidrolases/história , Venenos de Aranha/história , Animais , Catálise , História do Século XX , História do Século XXI , Humanos , Fosfolipase D/química , Fosfolipase D/farmacologia , Diester Fosfórico Hidrolases/química , Diester Fosfórico Hidrolases/farmacologia , Proteômica , Proteínas Recombinantes/farmacologia , Picada de Aranha/diagnóstico , Picada de Aranha/tratamento farmacológico , Picada de Aranha/enzimologia , Venenos de Aranha/química , Venenos de Aranha/farmacologiaRESUMO
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.
Assuntos
Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Dermatopatias/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Picada de Aranha/tratamento farmacológico , Animais , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Estrutura Molecular , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Coelhos , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , AranhasRESUMO
BACKGROUND: Loxoscelism is a common pathology in our environment with a broad spectrum of differential diagnoses and presentations, with potentially serious complications, even to the point of death. To date, there is no standard treatment for these patients. AIM: To describe the clinical manifestations, main complications, therapeutic management, and evolution of loxoscelism in an inpatient setting from a tertiary hospital in Chile. METHODS: All patients consulting and hospitalized in the hospital of the Pontificia Universidad Católica de Chile with diagnosis of loxoscelism between 2014 to 2017 and evaluated by dermatologist were included. Review of clinical files, including symptoms, images, laboratory parameters and treatment. RESULTS: We evaluated seventeen inpatient with loxoscelism, whose presentation responds to the national epidemiological pattern. Most cases were managed with antibiotics, systemic corticosteroids, antihistamines, and dapsone. From these, 11.8% corresponded to viscerocutaneous loxoscelism, successfully managed with supportive measures, systemic corticosteroids and antihistamines. Fifty-nine percent healed their cutaneous lesions after one month of treatment, with slight residual scarring or post inflammatory hyperpigmentation, without associated mortality in our series. DISCUSSION: Most cases of cutaneous loxoscelism presented excellent response and rapid resolution of the disease after combined therapy with systemic corticosteroids, antibiotics and dapsone, suggesting that the use of these therapies could stop the progression of cutaneous necrosis and prevent complications associated with loxoscelism.
Assuntos
Dermatopatias/etiologia , Picada de Aranha/complicações , Venenos de Aranha/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Picada de Aranha/diagnóstico , Picada de Aranha/tratamento farmacológico , Vísceras/patologia , Adulto JovemRESUMO
Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated with antivenom. Current antivenoms are based on plasma-derived immunoglobulins or immunoglobulin fragments from hyper-immunized animals. Although these medicines have been life-saving for more than 120 years, opportunities to improve envenoming therapy exist. In the later decades, new biotechnological tools have been applied with the aim of improving the efficacy, safety, and affordability of antivenoms. Within the avenues explored, novel immunization strategies using synthetic peptide epitopes, recombinant toxins (or toxoids), or DNA strings as immunogens have demonstrated potential for generating antivenoms with high therapeutic antibody titers and broad neutralizing capacity. Furthermore, these approaches circumvent the need for venom in the production process of antivenoms, thereby limiting some of the complications associated with animal captivity and venom collection. Finally, an important benefit of innovative immunization approaches is that they are often compatible with existing antivenom manufacturing setups. In this review, we compile all reported studies examining venom-independent innovative immunization strategies for antivenom development. In addition, a brief description of toxin families of medical relevance found in snake, scorpion, and spider venoms is presented, as well as how biochemical, bioinformatic, and omics tools could aid the development of next-generation antivenoms.
Assuntos
Antivenenos/administração & dosagem , Antivenenos/biossíntese , Mordeduras de Serpentes/tratamento farmacológico , Picada de Aranha/tratamento farmacológico , Animais , Antivenenos/imunologia , Humanos , Venenos de Serpentes/imunologia , Venenos de Aranha/imunologiaRESUMO
Diagnostic tests for arachnid accidents remain unavailable for patients and clinicians. Together with snakes, these accidents are still a global medical concern, and are recognized as neglected tropical issues. Due to arachnid toxins' fast mechanism of action, quick detection and quantification of venom is required to accelerate treatment decisions, rationalize therapy, and reduce costs and patient risks. This review aims to understand the current limitations for arachnid venom identification and quantification in biological samples. We benchmarked the already existing initiatives regarding test requirements (sample or biomarkers of choice), performances (time, detection limit, sensitivity and specificity) and their validation (on animal models or on samples from envenomed humans). Our analysis outlines unmet needs for improving diagnosis and consequently treatment of arachnid accidents. Hence, based on lessons from past attempts, we propose a road map for raising best practice guidelines, leading to recommendations for future progress in the development of arachnid diagnostic assays.
Assuntos
Picada de Aranha/diagnóstico , Venenos de Aranha/análise , Animais , Antivenenos/uso terapêutico , Bioensaio , Testes Diagnósticos de Rotina , Humanos , Picada de Aranha/tratamento farmacológicoRESUMO
Resumen Introducción: El loxoscelismo es una patología frecuente en nuestro medio con un amplio espectro de presentaciones y diagnósticos diferenciales, con complicaciones potencialmente graves, e incluso con riesgo de muerte. A la fecha no existe un tratamiento estándar para estos pacientes. Objetivo: Describir las manifestaciones clínicas, principales complicaciones, manejo terapéutico y evolución de pacientes internados por loxoscelismo en un hospital terciario en Chile. Pacientes y Método: Se analizaron todos los pacientes consultantes e internados por loxoscelismo en el Hospital Clínico de la Pontificia Universidad Católica de Chile entre los años 2014 y 2017, evaluados en interconsulta por Dermatología. Revisión de los registros clínicos incluyendo semiología, imágenes, informes de laboratorio y tratamientos efectuados. Resultados: Se registraron 17 casos de loxoscelismo de manejo hospitalario, cuya presentación responde al patrón epidemiológico nacional. La mayoría de los casos fue manejada con antimicrobianos, corticosteroides sistémicos, antihistamínicos y dapsona. De ellos, 11,8% correspondieron a loxoscelismo cutáneo visceral, manejados exitosamente con medidas de soporte, corticosteroides sistémicos y antihistamínicos. El 59% presentó resolución de las lesiones al mes de tratamiento, con cicatriz residual leve o hiperpigmentación postinflamatoria, sin mortalidad en nuestra serie. Discusión: La mayoría de los casos de loxoscelismo cutáneo presentó excelente respuesta y rápida resolución del cuadro tras el tratamiento asociado de corticosteroides sistémicos, antimicrobianos y dapsona, sugiriendo que el uso de estas terapias podría detener la progresión de la necrosis cutánea y prevenir las complicaciones asociadas al loxoscelismo.
Background: Loxoscelism is a common pathology in our environment with a broad spectrum of differential diagnoses and presentations, with potentially serious complications, even to the point of death. To date, there is no standard treatment for these patients. Aim: To describe the clinical manifestations, main complications, therapeutic management, and evolution of loxoscelism in an inpatient setting from a tertiary hospital in Chile. Methods: All patients consulting and hospitalized in the hospital of the Pontificia Universidad Católica de Chile with diagnosis of loxoscelism between 2014 to 2017 and evaluated by dermatologist were included. Review of clinical files, including symptoms, images, laboratory parameters and treatment. Results: We evaluated seventeen inpatient with loxoscelism, whose presentation responds to the national epidemiological pattern. Most cases were managed with antibiotics, systemic corticosteroids, antihistamines, and dapsone. From these, 11.8% corresponded to viscerocutaneous loxoscelism, successfully managed with supportive measures, systemic corticosteroids and antihistamines. Fifty-nine percent healed their cutaneous lesions after one month of treatment, with slight residual scarring or post inflammatory hyperpigmentation, without associated mortality in our series. Discussion: Most cases of cutaneous loxoscelism presented excellent response and rapid resolution of the disease after combined therapy with systemic corticosteroids, antibiotics and dapsone, suggesting that the use of these therapies could stop the progression of cutaneous necrosis and prevent complications associated with loxoscelism.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Picada de Aranha/complicações , Dermatopatias/etiologia , Venenos de Aranha/efeitos adversos , Picada de Aranha/diagnóstico , Picada de Aranha/tratamento farmacológico , Estações do Ano , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Vísceras/patologia , Estudos RetrospectivosRESUMO
La mordedura por araña del género Loxosceles produce dermonecrosis en el sitio de la lesión y complicaciones sistémicas secundarias a reacciones enzimáticas de su veneno, lo que aumenta la tasa de mortalidad. El objetivo es reportar cuatro casos de loxoscelismo atendidos en el hospital General San Juan de Dios, donde los pacientes tuvieron una evolución satisfactoria a pesar de la inexistencia del antiveneno como manejo ideal de la toxicidad (AU)
Assuntos
Humanos , Feminino , Picada de Aranha/tratamento farmacológico , Venenos de Aranha/efeitos adversos , Aranha Marrom Reclusa/patogenicidade , Hemólise , GuatemalaRESUMO
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.