Evolución clínica de pacientes con loxoscelismo sistémico y dermonecrótico en un hospital de tercer nivel / Clinical evolution of patients with systemic and dermonecrotic loxoscelism in a third level hospital

Resumen ANTECEDENTES: el loxoscelismo es una intoxicación por la mordedura de la araña Loxosceles reclusa, cuyo veneno contiene esfingomielinasa-D, causante de hemólisis y necrosis. Se reporta una serie de casos que describen su evolución clínica y respuesta al tratamiento. OBJETIVO: describir la evolución y características clínicas de pacientes con loxoscelismo sistémico y dermonecrótico, su respuesta al tratamiento y las complicaciones. PACIENTES Y MÉTODO: estudio que incluyó el análisis descriptivo de pacientes tratados en el servicio de Medicina Interna, Unidad Médica de Alta Especialidad Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, de 2010 a 2015. RESULTADOS: se atendieron ocho hombres (67%) y cuatro mujeres (33%), con edad media de 39.4 años (16-83 años). El sitio de mordedura en cinco casos (42%) fue el miembro pélvico izquierdo; cuatro casos en el miembro torácico derecho (33%), dos en la cara (17%) y uno en el miembro torácico izquierdo (9%). Nueve casos provenían del Estado de México, dos de la Ciudad de México y uno de Hidalgo. Manifestación clínica: flictenas (cinco casos), edema y eritema (tres), placa liveloide (tres) y necrosis (un caso). Nueve (75%) pacientes se trataron inicialmente en la unidad de cuidados intensivos. Se reportaron las siguientes complicaciones sistémicas: renales (67%), pulmonares con administración de aminas (33%) y hematológicas (8%). Diez casos recibieron faboterápico, con media de 1.5 viales (0 a 4); cinco casos (42%) recibieron dapsona y cuatro de ellos (33%) padecieron metahemoglobinemia; once (92%) pacientes requirieron lavado-desbridación y 7 (58%) injerto cutáneo; cuatro pacientes (33%) tuvieron infección agregada de la herida. El promedio de estancia hospitalaria fue 16.2 días (3 a 40 días). CONCLUSIÓN: la evolución y pronóstico de esta afección depende de una sospecha inicial, diagnóstico y tratamiento oportunos. El loxoscelismo debe incluirse en los diagnósticos diferenciales de lesiones necróticas y progresivas, con o sin afección sistémica.

Abstract BACKGROUND: Loxoscelism is a poisoning caused by the bite of Loxosceles recluse spider, whose venom contains sphingomyelinaseD, causing hemolysis and necrosis. We report a case series describing their clinical course and response to treatment. OBJECTIVE: To describe the evolution and clinical characteristics of patients with systemic and dermonecrotic loxoscelism, their response to treatment and complications. PATIENTS AND METHOD: A descriptive analysis of patients treated in the Internal Medicine Service, Centro Médico Nacional La Raza, from 2010 to 2015. RESULTS: A total of 8 men (67%) and 4 women (33%) were included. Mean age was 39.4 years (16-83 years). Bite site was left pelvic limb in 5 cases (42%), 4 in the right forelimb (33%), 2 in the face (17%) and 1 in left forelimb (9%). Nine cases came from Estado de México, 2 from Mexico City and 1 from Hidalgo. Initial manifestations included blisters (five cases), edema and erythema (three cases), liveloide plate (three cases) and necrosis (one case). Nine (75%) patients were initially managed in ICU. Systemic complications were renal (67%), lung with use of amines (33%) and hematological (8%). Ten cases were treated with fabotherapy, with an average of 1.5 vials (0-4). Five cases (42%) received dapsone and 4 of them (33%) developed methemoglobinemia. Eleven (92%) required surgical washing and debridement and 7 (58%) skin graft; four patients (33%) had secondary wound infection. Average hospital stay was 16.2 days (3-40 days). CONCLUSIONS: The evolution and prognosis depends on initial suspicion early diagnosis and treatment. Loxoscelism should be included in the differential diagnosis of progressive necrotic lesions, with or without systemic involvement.

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.