Cutaneous-hemolytic loxoscelism following brown recluse spider envenomation: new understandings.

Background: Brown recluse spider (BRS) (Loxosceles reclusa) envenomation can cause local dermonecrotic lesions, constitutional symptoms, and potentially fatal hemolysis (i.e., cutaneous-hemolytic loxoscelism). As the incidence of hemolysis is low and the spider habitat is limited, little is known regarding the clinical course of cutaneous-hemolytic loxoscelism.Methods: We performed a retrospective observational study of patients following BRS envenomation over an eight-year period. Demographics, clinical course, laboratories, and interventions were assessed. Wilcoxon rank-sum tests and Pearson chi-square tests were used in the univariate analyses. Logistic regression assessed the independent contribution of symptoms in a multivariate analysis.Results: Of the 97 patients, 40.2% (n = 39) developed hemolysis; the majority (66.7%) were 18 years old or younger. Univariate analysis revealed that constitutional symptoms were associated with hemolysis, but multivariate analysis showed only myalgia (aOR: 7.1; 95% CI: 2.2-22.7; p < .001) and malaise (aOR: 12.76; 95% CI: 1.4-119.9; p = .026) were independently associated with hemolysis. The median time to hemolysis onset was 1.0 days (IQR: 1.0-2.5) and all occurred within a week of envenomation. Hemolysis durations were longer in patients DAT positive for IGG antibodies (7.5 vs. 4.0 days; p = .042). Most (76.9%) of hemolyzing patients received blood. In patients with cutaneous-hemolytic loxoscelism, hematuria occurred in 32.4%, rhabdomyolysis occurred in 60.9%, and elevated transaminases with normal hepatic synthetic function occurred in 29.4% but all of these patients developed rhabdomyolysis. Hemolysis was both intravascular and extravascular. Complications (hyperkalemia, INR ≥2.0, metabolic acidosis requiring bicarbonate, hypotension requiring vasopressors, and hypoxia requiring intubation) occurred only in patients with profound hemolytic anemia (hemoglobin <4 g/dL); one patient died.Conclusions: Constitutional symptoms occur in both cutaneous and cutaneous-hemolytic loxoscelism, although they occur more frequently in patients who develop hemolysis. Children may be at a higher risk of hemolysis after envenomation. Renal involvement (as evidenced by hematuria) and rhabdomyolysis may occur more frequently than has been previously reported. Hemolysis was both intravascular and extravascular.

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

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

Probable cutaneous loxoscelism with mild systemic symptoms: A case report from Spain.

We present a case from Valencia, Spain, of a 25-year-old woman who presented with a painful erythematous skin lesion, initially diagnosed as cellulitis. The lesion was unresponsive to antibiotic treatments and progressed into a hemorrhagic blister with necrotic ulcer formation. Posterior collection of a spider from the patient's home and expert identification of the spider as Loxosceles rufescens was achieved, establishing the diagnosis of probable cutaneous loxoscelism. Symptomatic treatment, general wound care and ultimately surgery, resulted in complete recovery with minor residual scarring. This case illustrates some of the difficulties encountered in the diagnosis and treatment of loxoscelism and adds to the increasing reports of loxoscelism in the Mediterranean Basin.

Clinical consequences of toxic envenomation by spiders.

Spider venom is being researched for its potential use in applications such as insecticides, to better understand the dynamics of neuronal ion channel physiology and as potential remedies to counter antibiotic resistant bacteria. However, spider venom is more widely known for its ability to cause deleterious reactions after toxic envenomations in humans. In this short review, the "dark" side of spider venoms is presented to provide a counterbalance to the investigations of the positive potential that venoms can or might improve our world or its understanding. The goal was to present a short primer on species having clinical consequences in humans rather than be an exhaustive review of all spiders of medical importance.

Manifestaciones de neurotoxicidad en el envenenamiento por mordedura de araña «viuda negra» en edades pediátricas / Neurotoxic manifestations of black widow spider envenomation in paediatric patients

Introducción: El envenenamiento por mordedura de araña «viuda negra» (Latrodectus mactans) en niños se expresa clínicamente con neurotoxicidad. Objetivo: Identificar los signos y síntomas neurológicos característicos, en las diferentes edades pediátricas, la evolución y el tratamiento en pacientes atendidos por esta mordedura de en un hospital pediátrico de noroeste México. Material y métodos: Se revisaron 70 expedientes de niños hospitalizados entre 1978-2014; estableciéndose 2 grupos: grupo 1, de 33 lactantes y preescolares, y grupo 2, con 37 escolares y adolescentes. Las variables consideradas fueron: edad, género, lugar de procedencia, sitio del accidente, área corporal afectada, grado de envenenamiento, tratamiento, evolución clínica, diferencias estadísticas. Resultados: Predominó el género masculino, 61,4%; los lactantes menores de un año fueron un 14,2%. El 70% de los pacientes tuvieron el contacto con el arácnido dentro del domicilio; las áreas anatómicas más afectadas fueron miembros inferiores, cuello, tronco y abdomen; los signos y síntomas neurológicos más notables en el grupo 1 fueron: irritabilidad, llanto constante, naáseas, sialorrea, agitación, taquicardia, arritmias, incapacidad para caminar, espasmos musculares, parestesias, tetania, convulsiones, nistagmo. En el grupo 2 fueron: dolor local, cefalea, sialorrea, parestesias, sudoración profusa, ansiedad, debilidad muscular, espasmos musculares y temblor fino. La manifestación clínica autonómicas predominante en el grupo 1 fue sialorrea, p < 0,0001, y en el grupo 2, parestesias, p < 0,0001. El uso de faboterápicos en el tratamiento permitió mejor evolución, menor tiempo de hospitalización, no hubo mortalidad. Conclusiones: Los signos y los síntomas de la mordedura por araña «viuda negra» son predominantemente autonómicos; identificarlos permite el diagnóstico oportuno y tratamiento eficaz

Introduction: Envenomation by black widow spiders manifests clinically with signs of neurotoxicity in paediatric patients. Objective: Identify typical neurological signs and symptoms in paediatric patients of different ages, and describe treatment and outcomes in a paediatric hospital in northwest Mexico. Material and methods: We reviewed 70 clinical records of patients hospitalised due to black widow spider bite between 1978 and 2014. We divided the total into 2 groups: Group 1, infants and preschool children; and Group 2, school-age children and adolescents. The demographic variables were age, sex, birthplace, place where envenomation occurred, body part(s) affected, degree of envenomation according to signs and symptoms, treatment, clinical outcome, and statistical differences. Results: Boys accounted for 61.4% of all cases, and infants younger than one year old made up 14.2%. Most patients (70%) were bitten by the spider at home; the anatomical areas most frequently affected were the legs, neck, thorax, and abdomen. The neurological signs and symptoms displayed by Group 1 were irritability, constant crying, sialorrhoea, nausea, tachycardia, arrhythmias, fatigue when walking, agitation, muscle spasms paraesthesia, tetany, seizures, and nystagmus. Signs in Group 2 included localized pain, headache, sialorrhoea, paraesthesia, profuse sweating, anxiety, muscle weakness, muscle spasms, and fine tremor. The predominant autonomic sign in Group 1 was sialorrhoea (P<.0001) and in Group 2, paraesthesia (P<.0001). Patients who received Fab antivenom treatment displayed better outcomes and shorter hospital stays than those who did not. No deaths were reported. Conclusions: The neurological signs and symptoms caused by black widow spider bite are predominantly autonomic, and identifying them permits early diagnosis and more effective treatment

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

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.

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.

Accidents caused by Phoneutria nigriventer: diagnosis and nursing interventions / Acidentes causados por Phoneutria nigriventer: diagnósticos e intervenções de enfermagem / Accidentes causados por Phoneutria nigriventer: diagnósticos e intervenciones de enfermería

Objetivo: Identificar os principais rótulos diagnósticos de enfermagem e suas respectivas intervenções de enfermagem, através das principais manifestações clínicas apresentadas pelos indivíduos intoxicados pelo veneno da aranha Phoneutria ningriventer encontradas na literatura. Método: Revisão integrativa da literatura consultada nas bases de dados PubMed e BVS, publicações impressas e sites oficiais relacionados à temática. Os rótulos diagnósticos de enfermagem foram elaborados com base na taxonomia II da North American Nursing Diagnosis Association International e o planejamento das intervenções de enfermagem de acordo com a Classificação das Intervenções de Enfermagem. Resultados: A partir dos achados, foi possível identificar oito rótulos diagnósticos e suas respectivas intervenções de enfermagem. Conclusão: Foram encontrados poucos estudos na literatura abordando as manifestações clínicas apresentadas pelos indivíduos intoxicados pelo veneno da aranha Phoneutria nigriventer e da atuação da enfermagem frente a esses casos.

Objective: To identify the main nursing diagnostic labels and the respective interventions through the main clinical manifestations presented by individuals poisoned by the venom of the spider Phoneutria nigriventer found in the literature. Method: Integrative review of literature consulted in PubMed and BVS databases, printed publications and official websites related to the theme. The nursing diagnostic labels were developed based on taxonomy II from the American Nursing Diagnosis Association International and the planning of nursing interventions in accordance with the Nursing Interventions Classification. Results: From the findings, it was possible to identify eight diagnostic labels and the respective nursing interventions. Conclusion: We found few studies addressing the clinical manifestations presented by individuals poisoned by the venom of the spider Phoneutria nigriventer and nursing performance in these cases.

Objetivo: Identificar las principales etiquetas diagnósticas de enfermería y sus respectivas intervenciones a través de las principales manifestaciones clínicas que presentan las personas intoxicadas por el veneno de la araña Phoneutria nigriventer encontradas en la literatura. Método: Revisión Integral de la literatura consultada en los bancos de datos PubMEed y BVS, publicaciones impresas y sitios web oficiales sobre el tema. Las etiquetas diagnósticas de enfermería fueron elaboradas con base en la taxonomía II de la North American Nursing Diagnosis Association International y planeamiento de las intervenciones de enfermería de acuerdo con la Clasificación de Intervenciones de Enfermería. Resultados: A través de los resultados fue posible identificar ocho etiquetas de diagnóstico y las respectivas intervenciones de enfermería. Conclusión: Se encontraron pocos los estudios de las manifestaciones clínicas que presentan las personas envenenadas por el veneno de la araña Phoneutria nigriventer y la actuación de enfermería en estos casos.

Reversible myocarditis after spider bite.

Black widow spiders (Latrodectus tredecimguttatus) are poisonous spiders endemic in Turkey. Latrodectus bites may cause myocarditis with increased cardiac enzymes. We treated two men (aged 20 and 33 years) who had myocarditis after black spider bites with leucocytosis and elevated levels of troponin I, creatine kinase and creatine kinase-MB fraction. Both patients had normal results on an ECG, and one patient had abnormal echocardiography with minimal left ventricular wall movement disorder. Both patients were hospitalised in the intensive care unit and treated with intravenous fluids, analgesics, spasmolytic drugs, tetanus prophylaxis and cardiac monitoring. The levels of troponin I, creatine kinase and creatine kinase-MB fraction improved, and the patients were discharged home on the third and fifth hospital day without complications. Myocarditis after a Latrodectus bite is rare, but may be associated with serious complications. Therefore, in regions endemic with Latrodectus spiders, prudent treatment of spider bites may include cardiac evaluation and monitoring.

Expressão do fator de crescimento endotelial vascular (VEGF) e seus receptores Flt-1 e Flk-1 após envenenamento pela aranha Phoneutria nigriventer em ratos / Expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 after envenoming by Phoneutria nigriventer spider in rats

O fator de crescimento endotelial vascular (VEGF), o principal regulador da angiogênese e da permeabilidade vascular, foi recentemente reconhecido como neurotrófico, neurogênico e neuroprotetor, sendo, portanto, regulado positivamente em muitos processos neuropatológicos. Neste modelo experimental de quebra da barreira hematoencefálica (BHE) pelo veneno da aranha Phoneutria nigriventer (PNV), a expressão do VEGF e seus receptores tirosina-quinase, Flt-1 e Flk-1 e de seus RNAs mensageiros foi investigada no hipocampo e cerebelo de ratos Wistar (Rattus norvegicus) por imunohistoquímica (IHQ), western blotting (WB) e reação em cadeia da polimerase em tempo real (qPCR). Paralelamente, a integridade da BHE foi avaliada através da expressão das proteínas da via paracelular, Ocludina e β-catenina, e da principal proteína da membrana basal, a Laminina, que estão presentes no endotélio na interface sangue-cérebro. O estudo foi realizado em ratos de 14 dias (neonatos) e de 8-10 semanas (adultos jovens) para avaliar diferenças em função da idade na funcionalidade da BHE e na possível mediação dos efeitos neurotóxicos do PNV pelo VEGF. A via escolhida para administração de PNV (1,7 mg/kg em 0,5ml de salina 0,9%) foi intraperitoneal, devido sua administração mais favorável nos animais neonatos. Os tempos de 2, 5 e 24 horas após a administração de PNV visaram investigar a expressão das proteínas, RNAs mensageiros e uma possível mediação pelo VEGF na fase aguda do envenenamento. A administração do PNV provocou sinais imediatos de intoxicação nos animais, os quais foram mais severos e imediatos nos neonatos do que nos adultos.

Vascular endothelial growth factor (VEGF), a major regulator of developmental angiogenesis and vascular permeability, was recently recognized as neurotrophic, neurogenic and neuroprotector, hence being upregulated in many neuropathological processes. In this experimental model of blood brain barrier (BBB) breakdown by the Phoneutria nigriventer spider venom (PNV), the expression of VEGF and its receptor tyrosine kinases, Flt-1 and Flk-1 and their mRNAs was investigated in the hippocampus and cerebellum of Wistar rats (Rattus norvegicus) by immunohistochemistry (IHC), western blotting (WB) and real time polymerase chain reaction (qPCR). Simultaneously, the BBB integrity was assessed through expression of paracellular pathway proteins, β- catenin and Occludin, and the main basement membrane protein, Laminin, which are present in the endothelium blood-brain interface. The study was performed in rats by 14 days (neonates) and 8-10 weeks (young adults) to assess differences related to age in the BBB functionality and the possible mediation of the PNV neurotoxic effects by VEGF. The via chosen for PNV administration (1.7 mg/kg in 0.5 ml of 0.9% saline) was intraperitoneally, due to more favorable application in neonate animals. The times of 2, 5 and 24 hours after PNV administration aimed to investigate the expression of proteins, mRNAs, and possible mediation by VEGF in acute envenomation. The PNV administration provoked immediate signs of intoxication in animals, which were more severe and immediate in neonates than in adults. In hippocampus, the WB data showed increased expression of VEGF, Flt-1 and Flk-1 and their mRNAs, which were concomitant with the development of perivascular edema, and decreased expression of Occludin, β-catenin and Laminin. IHC data show that VEGF immunoreactivity occurred in the bodies and dendrites of pyramidal neurons in the subfield CA1, CA2, CA3 and dentate gyrus of the hippocampus, in contrast with nuclear staining of Flt-1 and Flk-1.

Black widow spider (Latrodectus mactans) antivenom in clinical practice.

Black widow spider (Latrodectus mactans) envenomation has been recognized since antiquity. The syndrome, latrodectism, is characterized by painful muscle rigidity and autonomic disturbances such as tachycardia, hypertension, and diaphoresis. Symptoms typically last for 1-3 days. Treatment has ranged from local folk remedies to administration of specific antivenom. Opioid analgesics combined with muscle relaxants, such as benzodiazepines, are only effective at symptomatic and temporary control. Antivenom is by far the most efficacious therapy available based on symptom resolution, need for subsequent therapy, and hospital admission rates. Fear of allergic type reactions from antivenom administration has limited its use in the United States. A new purified F(ab)2 fragment Latrodectus mactans antivenom, Analatro®, is currently undergoing clinical trials. The product is expected to have similar efficacy and be associated with fewer adverse reactions when compared to the currently available partially purified whole IgG Merck product. This shift in the risk-benefit analysis may ultimately lead to more antivenom administration in significantly envenomated patients.