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

ABSTRACT 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).

Factores asociados al conocimiento y medidas preventivas de mordedura de Loxosceles laeta en la población de la Encuesta Nacional de Programas Presupuestales (ENAPRES) en el Perú 2017-2019

Introducción: Las enfermedades metaxénicas y zoonóticas, son consideradas prioridades nacionales de investigación en salud en Perú 2019-2023. De estas, los casos reportados por loxoscelismo han ido aumentando progresivamente. Objetivo: Determinar los factores asociados al conocimiento y medidas preventivas de mordedura de Loxosceles laeta en la población de la ENAPRES en el Perú 2017-2019. Métodos: Estudio de tipo observacional, transversal, analítico y retrospectivo, basado en la información de la ENAPRES. Resultados: Se analizó una muestra total de 285.354 personas. De estas, aquellos con 60 a más años (RPa=1,48; IC95%: 1,45-1,51), los costeños (RPa=1,37; IC95%: 1,33-1,40), las mujeres (RPa=1,12; IC95%: 1,11-1,13), con primaria o secundaria (RPa=1,12; IC95%: 1,09-1,15), con viviendas inadecuadas [techo (RPa=1,07; IC95%: 1,05-1,10), piso (RPa=1,02; IC95%: 1,00-1,04)], se asociaron con mayor posibilidad de tener más conocimiento sobre mordedura de L. laeta. Por otra parte, los encuestados de 60 a más años (RPa=1,49; IC95%: 1,46-1,52), los costeños (RPa=1,39; IC95%: 1,35-1,43), con estudios superiores no universitarios (RPa=1,19; IC95%: 1,15-1,22), las mujeres (RPa=1,13; IC95%: 1,12-1,14) y con viviendas con techos inadecuados (RPa=1,07; IC95%: 1,05-1,10) se asociaron con mayor posibilidad de realizar adecuadas medidas preventivas. En ambas, se halló asociación con el desechar los residuos orgánicos en calle o vía pública (RPa=0,97; IC95%: 0,96-0,99). Conclusiones: Se encontró aquellos factores asociados a conocimientos y a las medidas preventivas de mordedura de L. laeta.

Background: Metaxenic and zoonotic diseases are one of the ten national priorities for health research in Peru 2019-2023. Of these, the cases reported by loxoscelism have been increasing progressively. Aim: To determine the factors associated with the knowledge and preventive measures of Loxosceles laeta bite in the population of the ENAPRES in Peru 2017-2019. Methods: Observational, cross-sectional, analytical and retrospective study, based on information from ENAPRES. Results: A total sample of 285,354 people was analyzed. Of these, those aged 60 or over (PRa=1,48; 95%CI: 1,45-1,51), those from the coast (PRa=1,37; 95%CI: 1,33-1,40), women (PRa=1,12; 95%CI: 1,11-1,13), with primary or secondary education (PRa=1,12; 95%CI: 1,09-1,15), with inadequate housing [ceiling (PRa=1,07; 95%CI: 1,05-1,10), floor (PRa=1,02; 95%CI: 1,00-1,04)], were associated with higher possibility ofhaving more knowledge about L. laeta bite. On the other hand, those aged 60 or over (PRa=1,49; 95%CI: 1,46-1,52), those from the coast (PRa=1,39; 95%CI: 1,35-1,43), with non-university higher education (PRa=1,19; 95%CI: 1,15-1,22), women (PR a=1,13; 95%CI: 1,12-1,14) and with inadequate housing ceilings (PRa=1,07; 95%CI 1,05-1,10) were associated with a greater possibility of taking adequate preventive measures. In both, an association was found between disposing of organic waste on the street or on public roads (RPa=0.97; 95%CI: 0.96-0.99) Conclusions: It were found factors associated with knowledge and preventive for L. laeta bite.

Primer registro de un caso de loxoscelismo cutáneo ocasionado por mordedura de araña violinista (Loxosceles yucatana) en Yucatán, México / First record of a case of cutaneous loxoscelism caused by violin spider (Loxosceles yucatana) bite in Yucatan, Mexico

El loxoscelismo es ocasionado cuando el veneno dermonecrótico producido por las arañas del género Loxosceles, conocidas como «arañas violinistas», ingresa al organismo de una persona a través de su mordida. En México ocurre un subregistro de los casos de loxoscelismo por la ausencia de pruebas de laboratorio para su diagnóstico y la dificultad del cuadro clínico. El objetivo de este trabajo es describir un caso de loxoscelismo cutáneo ocasionado por mordedura de Loxosceles yucatana en un residente de Yucatán, México. El loxoscelismo cutáneo es el tipo más frecuente y menos severo. El presente caso se diagnosticó por medio de la sintomatología registrada en la historia clínica, la lesión inicial y la identificación de arañas L. yucatana. Este trabajo representa la primera descripción de un caso de loxoscelismo cutáneo con resolución favorable en Yucatán.

Loxoscelism occurs when the dermonecrotic venom produced by spiders of the genus Loxosceles, known as "violin spiders," enters a person's organism through their bite. In Mexico there is an underreporting of loxoscelism cases due to the absence of laboratory tests for its diagnosis and the complexity of the clinical picture. The aim of this paper is to describe a case of cutaneous loxoscelism caused by the bite of Loxosceles yucatana in a resident of Yucatan, Mexico. Cutaneous loxoscelism is the most frequent and less severe type. This case was diagnosed by means of the symptomatology registered in the medical records, the initial lesion, and the identification of L. yucatana spiders. This study represents the first description of a case of cutaneous loxoscelism with favorable outcome in Yucatan.

Temporal evolution of dermonecrosis in loxoscelism assessed by photodocumentation

ABSTRACT Background: Although loxoscelism (bites by brown spiders of the genus Loxosceles) frequently results in dermonecrosis, no previous clinical reports have provided detailed temporal photodocumentation of the evolution of dermonecrotic lesions in a case series. Methods This was a retrospective cohort study involving a case series of loxoscelism. Only cases of dermonecrosis with photodocumentation of lesion evolution (from admission until complete or almost complete healing) were included. Results: Eight patients (six men, two women; median age, 38 years) fulfilled the inclusion criteria. The bite sites included the thigh (n = 4), forearm (n = 2), abdomen (n = 1), and trunk (n = 1). Time interval between the bite and first contact with our service ranged from 15 to 216 h (median = 29 h). The main clinical manifestations included local erythematous and ischemic violaceous lesions overlying a base of indurated edema (livedoid plaque, 8), local pain (8), exanthema (6), serohemorrhagic vesicles/blisters (5), fever (5), and jaundice (1). Based on a previously established classification, the cases were classified as probable cutaneous-necrotic loxoscelism (CNL, n = 4), presumptive CNL (n = 3), and presumptive cutaneous-hemolytic loxoscelism (n = 1). Seven patients were treated with anti-arachnidic antivenom (AV; median time post-bite = 46 h). Complete lesion healing ranged from 34 to 98 days post-bite (median, 68 days; six patients). None of the patients required reconstructive plastic surgery. Conclusions The sequential photographic documentation showed considerable variation in the process of wound healing, with complete epithelialization requiring up to 3 months after the bite.

Síndrome compartimental agudo como complicación de un loxoscelismo cutáneo edematoso / Acute compartment syndrome as a complication of cutaneous loxoscelism mainly edematous

Resumen El síndrome compartimental agudo (SCA) es el aumento de la presión en un espacio osteofascial cerrado. Esto reduce la presión capilar bajo el nivel necesario para la viabilidad de los tejidos del compartimento. El SCA de mano como complicación de un loxoscelismo cutáneo (LC) de predominio edematoso es muy poco frecuente. Presentamos el caso de una mujer de 22 años que presentó un SCA de la mano secundario a un LC y que requirió tratamiento quirúrgico de urgencia mediante una fasciotomía dorsal y palmar.

Abstract Acute compartment syndrome (ACS) is the increase of pressure in a closed osteofascial space. This reduces capillary perfusion below the level necessary for tissue viability. Injury could be irreversible if proper treatment is not performed. Hand ACS secondary to cutaneous loxoscelism with edematous predominance is extremely infrequent. We present a clinical case of a 22-year-old patient who started a hand compartment syndrome secondary to cutaneous loxoscelism (CL), requiring emergency surgical treatment with dorsal and palmar fasciotomy.

Effects of copaiba oil on dermonecrosis induced by Loxosceles intermedia venom

Accidents caused by spiders of the genus Loxosceles constitute an important public health problem in Brazil. The venom of Loxosceles sp induces dermonecrosis at the bite site and systemic disease in severe cases. Traditional medicine based on plant-derived products has been proven to reduce the local effects of envenomation. The present study verified the healing effects of copaiba oil on lesions induced by the venom of L. intermedia. Methods: Cutaneous lesions were induced on the backs of rabbits by intradermal injection of L. intermedia venom. Copaiba oil was applied topically 6 hours after injection; the treatment was repeated for 30 days, after which animal skins were removed and processed for histopathological analysis. Blood samples were also collected before and 24 hours after venom inoculation to measure the hematological parameters. Results: Compared to the control group, the platelet count was reduced significantly in all groups inoculated with venom, accompanied by a decreased number of heterophils in the blood. The minimum necrotic dose (MND) was defined as 2.4 μg/kg. Topical treatment with copaiba oil demonstrated a differentiated healing profile: large skin lesions were observed 10 days after venom inoculation, whereas formation of a thick crust, without scarring was observed 30 days after venom inoculation. Histopathological analysis showed no significant difference after treatment. Nevertheless, the copaiba oil treatment induced a collagen distribution similar to control skin, in marked contrast to the group that received only the spider venom injection. Conclusions: We conclude that copaiba oil may interfere in the healing process and thus propose it as a possible topical treatment for cutaneous lesions induced by L. intermedia venom.(AU)

Loxoscelismo cutáneo: paciente con múltiples picaduras y con contraindicación para sulfas. Reporte de un caso / Cutaneous Loxoscelism: Patient with multiple bites and contraindication to sulfa drugs. Case report

RESUMEN Presentamos el caso clínico de un paciente adulto joven que consultó por picaduras de araña loxosceles y sus crías, con antecedentes personales importantes de trastorno de ansiedad generalizada y alergia tipo anafilaxia severa por sulfas y AINES. El proceso presentó evolución tórpida inicial con aparición de nuevas lesiones incluso 15 días después del accidente y a pesar de haber utilizado varias alternativas farmacológicas reportadas en la literatura como útiles (colchicina, antihistamínicos, esteroides, anticoagulantes, antibióticos) no había tenido respuesta, hasta la utilización de oxigeno por cámara hiperbárica con la cual frenó la aparición de nuevas lesiones y mejoró la reepitelialización sin necesidad de intervenciones quirúrgicas, con evolución exitosa.

SUMMARY We report the case of a young adult patient who presented bites by Loxosceles spider and its hatchlings with a history of importance of such allergy anaphylaxis severe by sulfa drugs and NSAIDs, generalized anxiety disorder, who presented initial torpid with new lesions even 15 days after the accident and despite having used several pharmacological alternatives reported in the literature as useful (colchicine , antihistamines, steroids, blood thinners, antibiotics) had not been answered, to the use of oxygen for hyperbaric chamber with which brake the appearance of new and improved reepithelialization injury without surgery, with successful evolution.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

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.(AU)

de araña marrón (Loxosceles laeta). presentación de un caso / Brown spider (Loxosceles laeta) bite. presentation of a case

Se presentó un caso tratado en la Unidad Básica de Salud del poblado Pedras municipio Matoes Do Norte estado Maranhao Brasil, de una gestante de 32.4 semanas con lesión necrótica en la cara interna del muslo derecho provocado por la picadura de una araña marrón. Con el propósito de informar un caso de lesión producida por la picadura de este insecto y revisar la literatura médica se presentó este reporte sobre una gestante de 19 años donde el diagnóstico se estableció mediante estudio epidemiológico y características de la lesión siendo diagnosticada finalmente de loxoscelismo cutáneo, lesión producida por la picadura de araña marrón(AU)

It was presented a case in the Basic Health Unit of Pedras municipality Matoes Do Norte Maranhao Brazil, from a pregnant woman of 32.4 weeks with a necrotic lesion on the inner side of her right thigh caused by the bite of a brown spider. In order to report a case of injury caused by the brown spider bite and review the medical literature, this report is presented on a pregnant woman of 19 years where the diagnosis was established by epidemiological study and characteristics of the lesion being the final diagnosis of Loxoscelism cutaneous lesion produced by the brown spider bite(AU)

Experiencia en loxoscelismo cutáneo y cutáneo visceral de manejo hospitalario: clínica, evolución y propuesta terapéutica / Experience in visceral cutaneous and cutaneous loxoscelism of hospital management: clinical, evolution and therapeutic proposal

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.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

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.

Caracterización clínica del loxoscelismo dermonecrótico en equinos de córdoba, colombia / Clinical characterization of dermonecrotic loxoscelism in equine of Córdoba, Colombia / Caracterização clínica da loxoscelismo dermonecrótica em equinos de Córdoba, Colômbia

Resumen El objetivo de este estudio fue evaluar las características clínicas del loxoscelismo dermonecrótico (LDN) en equinos del departamento de Córdoba, Colombia. El estudio, fue de tipo descriptivo, no probabilístico, las muestra fueron seleccionadas por conveniencia. Se utilizaron nueve caballos criollos (Equus ferus caballus) y dos burros (Equus asinus africanus) con LDN diagnosticados clínica e histopatológicamente en diferentes producciones del Departamento. Al describir las lesiones cutáneas, éstas se caracterizaron por la presencia de una severa dermatitis necrótica, con edema y un área eritematosa focal, al detallar el área lesionada, se observó un punto necrótico central y dos halos alrededor (un halo blanco medial y un halo violáceo más externo) en la mayoría de los casos estudiados; así como ausencia de signos neurológicos y sistémicos. Las lesiones se ubicaron en la mayoría de los casos a nivel dorsal, seguido de la región rostral, pecho y pene. Histopatológicamente en la coloración de Hematoxilina Eosina (H&E), se observó severa dermatitis piogranulomatosa, con marcada infiltración de polimorfonucleares especialmente neutrófilos, con vacuolización de la capa basal de la epidermis y edema en la unión dermo-epidérmica. El diagnóstico definitivo de LDN en los 11 animales estudiados, se fundamentó en las manifestaciones clínicas observadas, las características anatomopatológicas de las lesiones y los resultados histopatológicos. El presente informe constituye el primer reporte de LDN en el Departamento de Córdoba, ya que no se encontraron reportes en la literatura consultada.

Abstract The aim of this study was to characterize the clinical aspects of dermonecrotic loxoscelism (LDN) in horses department of Cordoba, Colombia. This study was descriptive, not probabilistic, in animals of convenience. Nine horses (Equus ferus caballus) and 2 donkeys (Equus asinus africanus) were used with LDN diagnosed clinically and histopathologically in different productions of the Department. When describing the skin lesions, these were characterized by the presence of severe necrotic dermatitis, with edema and a focal erythematous area, when detailing the injured area, a central necrotic spot and two halos around it (a medial white halo and a halo Violet) in most of the cases studied; As well as absence of neurological and systemic signs. The lesions were located in most cases at the dorsal level, followed by the rostral region, chest and penis. Histopathologically in the staining of Hematoxylin Eosin (H & E), severe piogranulomatous dermatitis was observed, with marked infiltration of polymorphonuclear cells especially neutrophils, with vacuolization of the basal layer of the epidermis and edema in the dermo-epidermal junction. The definitive diagnosis of LDN in the 11 animals studied was based on the clinical manifestations observed, the anatomopathological characteristics of the lesions and the histopathological results. The present report constitutes the first LDN report in the Department of Córdoba, since no reports were found in the consulted literature.

Resumo O objetivo deste estudo foi caracterizar os aspectos clínicos da loxoscelismo dermonecrótica (LDN) em equinos de Córdoba, Colômbia. Este estudo foi descritivo, não probabilístico, em animais de conveniência. Foram usados 9 cavalos (Equus ferus caballus) e 2 jumentos (Equus asinus africanus) com LDN clinicamente e histologicamente diagnosticado no Departamento diferentes produções. Ao descrever as lesões da pele, que foram caracterizados pela presença de dermatite necrotizante grave, edema e focal área eritematosa, detalhando a área lesionada, um ponto necrótico central e dois halos foram observados em torno de (halo branco medial e halo mais exterior) violáceo, na maioria dos casos estudados; e ausência de sinais neurológicos e sistémicas. As lesões foram localizados na maioria dos casos ao nível dorsal, seguida da rostral, peito e do pénis. Foi observada histologicamente em hematoxilina-eosina (H & E), dermatite piogranulomatosa grave, com infiltração acentuada de neutrófilos polimorfonucleares especialmente com vacuolização da camada basal da epiderme e edema na junção dermo-epidérmica. O diagnóstico definitivo da LDN nos 11 animais estudados foi baseado nas manifestações clínicas observadas, características histopatológicas de lesões e os resultados histopatológicos. O presente relatório constitui o primeiro relatório LDN no Departamento de Córdoba, uma vez que não foram encontrados relatórios na literatura consultada.

Highlights in the knowledge of brown spider toxins

Abstract Brown spiders are venomous arthropods that use their venom for predation and defense. In humans, bites of these animals provoke injuries including dermonecrosis with gravitational spread of lesions, hematological abnormalities and impaired renal function. The signs and symptoms observed following a brown spider bite are called loxoscelism. Brown spider venom is a complex mixture of toxins enriched in low molecular mass proteins (440 kDa). Characterization of the venom confirmed the presence of three highly expressed protein classes: phospholipases D, metalloproteases (astacins) and insecticidal peptides (knottins). Recently, toxins with low levels of expression have also been found in Loxosceles venom, such as serine proteases, protease inhibitors (serpins), hyaluronidases, allergen-like toxins and histamine-releasing factors. The toxin belonging to the phospholipase-D family (also known as the dermonecrotic toxin) is the most studied class of brown spider toxins. This class of toxins single-handedly can induce inflammatory response, dermonecrosis, hemolysis, thrombocytopenia and renal failure. The functional role of the hyaluronidase toxin as a spreading factor in loxoscelism has also been demonstrated. However, the biological characterization of other toxins remains unclear and the mechanism by which Loxosceles toxins exert their noxious effects is yet to be fully elucidated. The aim of this review is to provide an insight into brown spider venom toxins and toxicology, including a description of historical data already available in the literature. In this review article, the identification processes of novel Loxosceles toxins by molecular biology and proteomic approaches, their biological characterization and structural description based on x-ray crystallography and putative biotechnological uses are described along with the future perspectives in this field.

Highlights in the knowledge of brown spider toxins

Abstract Brown spiders are venomous arthropods that use their venom for predation and defense. In humans, bites of these animals provoke injuries including dermonecrosis with gravitational spread of lesions, hematological abnormalities and impaired renal function. The signs and symptoms observed following a brown spider bite are called loxoscelism. Brown spider venom is a complex mixture of toxins enriched in low molecular mass proteins (4-40 kDa). Characterization of the venom confirmed the presence of three highly expressed protein classes: phospholipases D, metalloproteases (astacins) and insecticidal peptides (knottins). Recently, toxins with low levels of expression have also been found in Loxosceles venom, such as serine proteases, protease inhibitors (serpins), hyaluronidases, allergen-like toxins and histamine-releasing factors. The toxin belonging to the phospholipase-D family (also known as the dermonecrotic toxin) is the most studied class of brown spider toxins. This class of toxins single-handedly can induce inflammatory response, dermonecrosis, hemolysis, thrombocytopenia and renal failure. The functional role of the hyaluronidase toxin as a spreading factor in loxoscelism has also been demonstrated. However, the biological characterization of other toxins remains unclear and the mechanism by which Loxosceles toxins exert their noxious effects is yet to be fully elucidated. The aim of this review is to provide an insight into brown spider venom toxins and toxicology, including a description of historical data already available in the literature. In this review article, the identification processes of novel Loxosceles toxins by molecular biology and proteomic approaches, their biological characterization and structural description based on x-ray crystallography and putative biotechnological uses are described along with the future perspectives in this field.(AU)

Loxoscelismo cutáneo predominantemente edematoso: a propósito de un caso / Cutaneous loxoscelism mainly edematous: a case report

In Chile, loxoscelism is caused by the bite of the Loxosceles laeta spider. The clinical presentation has two different forms: cutaneous loxoscelism (CL) and vicero-cutaneous loxoscelism, which is less frequent. Cutaneous loxoscelism includes an uncommon clinical variation (4%), called CL with edematous predominance (CLEP). We present a 5-year-old patient with sudden pain and edema on his right eyelid associated with fever, which progressed rapidly involving the right hemifacial area, frontal region, and left eyelid. Angioedema and pre-orbital cellulitis were discarded and CLEP was suspect. Cutaneous loxoscelism with an edematous predominance is self-limited, benign and with little or no necrotic injury due to the edema, which dilutes the toxin-induced enzymatic process causing necrosis. As in the reported cases it usually responds well to medical treatment and does not cause visceral involvement.

El loxoscelismo en Chile es un cuadro producido por la mordedura de la araña Loxosceles laeta. Las formas de presentación son: loxoscelismo cutáneo (LC) y loxoscelismo cutáneo-visceral (LCV), el último menos frecuente. Dentro del LC existe una variante poco común (4%) conocida como loxoscelismo cutáneo predominantemente edematoso (LCPE). Nuestro caso es un paciente de 5 años que consultó por cuadro de inicio súbito de dolor y edema palpebral derecho, asociado a fiebre el cual evolucionó con rápida progresión extendiéndose en la hemicara derecha, región frontal y párpado izquierdo. Se descartó un angioedema y una celulitis periorbitaria, sospechándose un LCPE. Se manejó con hidrocortisona y clorfenamina. El LCPE es un cuadro benigno, autolimitado, en que no está presente la lesión necrótica o ésta es insignificante. Predomina el edema, el cual abortaría la necrosis al diluir el proceso enzimático producido por el veneno. Tiene buena respuesta al tratamiento médico, con ausencia de compromiso visceral.

Loxoscelismo cutáneo visceral: actualización en el manejo a propósito de un caso / Viscerocutaneous loxoscelism: case report and update on management

Loxoscelism is a condition produced by the bite of Loxosceles laeta. It can present as cutaneous loxoscelism with only vascular dermal manifestations or as viscerocutaneus loxoscelism with systemic compromise and a mortality rate of 1 to 3%. We report the case of an adult patient presenting viscerocutaneus loxoscelism, who was evolving with macrohematuria, edema, and progressive blisters, requiring treatment in the intensive care unit. He was treated according to the actual scientific evidence with antihistamines, corticosteroids, and dual antibiotic therapy covering Streptococcus spp., Staphylococcus spp., and anaerobes, particularly penicillin and tetracycline resistant C. perfringens. The use of dapsone and antiloxosceles-serum was avoided. The patient showed a favorable clinical evolution.

El loxoscelismo es producido por la mordedura de la araña Loxosceles laeta. Puede ser cutáneo, con alteraciones vasculares o cutáneo-visceral, con manifestaciones sistémicas y una mortalidad de 1 a 3%. Se presenta el caso de un paciente adulto con loxoscelismo cutáneo-visceral, que evolucionó con hematuria macroscópica, edema y aparición de flictenas en forma progresiva en antebrazo, requiriendo ser trasladado a la Unidad de Tratamiento Intermedio. Fue manejado según la evidencia científica actual que recomienda el uso de antihistamínicos, corticoesteroides y terapia antibacteriana asociada para la cobertura de Streptococcus spp., Staphylococcus spp. y bacterias anaerobias, especialmente C. perfringens resistente a penicilina y tetracilina, evitando el uso de dapsona y de suero anti-loxosceles. Evolucionó de manera favorable.

The history of venomous spider identification, venom extraction methods and antivenom production: a long journey at the Butantan Institute, São Paulo, Brazil

The article provides a historical report on venomous spider identification, venom obtainment methods and serum production at the Butantan Institute, São Paulo, Brazil. It is based on literature and personnal experience during the last 50 years. This result is the discovery that the real species causing potential severe human accidents were the spiders of the genus Loxosceles and Phoneutria.

The History of Venomous Spider Identification, Venom Extraction Methods and Antivenom Production: a Long Journey at the Butantan Institute, São Paulo, Brazil

The article provides a historical report on venomous spider identification, venom obtainment methods and serum production at the Butantan Institute, São Paulo, Brazil. It is based on literature and personnal experience during the last 50 years. This result is the discovery that the real species causing potential severe human accidents were the spiders of the genus Loxosceles and Phoneutria.(AU)

Desarrollo de cohortes y parámetros poblacionales de la araña del rincón Loxosceles laeta / Development and population parameters of cohorts of the Chilean recluse spider Loxosceles laeta

Background: Despite the abundant eco-epidemiological knowledge of the Chilean reclusive spider, Loxosceles laeta, which causes all forms of loxoscelism in Chile, the main characteristics of this species its stages of development remains poorly known especially in the medical area. Objective: In this study we address these issues with the goal of providing clear images of the development of this species and for the first time on population projections as well as the relationship between mature and immature instars, useful data for the control and prevention of accidental bites. Results: We found that L. laeta is an r-selected species, with R0 = 2.1, a generation time of G = 2.1 years, with a concentration of the reproductive value of females between the first and second year of life. We determined the average sizes and development times of all instars. The first vary between 2.3 mm at birth and about 13 mm at adulthood. The total development time was about 1 year. Discussion: The population projection by Leslie matrix suggested great capacity for growth and dispersal with clear seasonal population fluctuations associated with reproduction. It also showed that the proportion of immature varied seasonally between 80 and 90 %, which means that a house with three or four visible adult spiders actually has a population between 20 and 40 spiders in total.

Introducción: A pesar del abundante conocimiento eco-epidemiológico de la araña del rincón, Loxosceles laeta, causante de todos los cuadros de loxoscelismo en Chile, sigue siendo una especie poco conocida en el ambiente médico, especialmente las características y tiempos de sus estados de desarrollo. Objetivo: En este estudio abordamos estos aspectos con el objetivo de aportar imágenes claras del desarrollo de esta especie y por primera vez de sus características y proyecciones poblacionales y de la relación entre estados maduros e inmaduros, datos útiles para el control y prevención de los accidentes por mordedura. Resultados: Loxosceles laeta es una especie r-estratega, con un R0 = 2,1, un tiempo generacional G = 2,1 años y con concentración del valor reproductivo de las hembras entre el primer y segundo año de vida. Determinamos los tamaños promedio y los tiempos de desarrollo de todos los estados. Los primeros varían entre los 2,3 mm al nacer y alrededor de 13 mm al estado adulto. Los tiempos totales de desarrollo son de aproximadamente un año. Discusión: La proyección de la población con matriz de Leslie sugiere una gran capacidad de crecimiento y dispersión, pero con claras fluctuaciones poblacionales estacionales asociadas a la reproducción. Además se muestra que la proporción de estados inmaduros fluctúa estacionalmente entre 80 y 90%, lo que implica que una casa con tres o cuatro arañas adultas visibles, en realidad tiene una población entre 20 y 40 arañas en total.

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 Loxoscelesvenom agents.