Cuadros cutáneo-mucosos asociados al consumo de cocaína / Cutaneous and Mucosal Conditions Associated With Cocaine Use

El consumo de cocaína, junto con algunos de sus adulterantes más frecuentes como el levamisol, puede provocar múltiples procesos cutáneos y mucosos, ya sean de índole isquémico, dermatosis neutrofílicas, lesiones destructivas de la línea media y vasculitis asociadas a ANCA, entre otros. Generalmente no se asocia clínica sistémica llamativa.Todos estos cuadros pueden presentar anticuerpos antinucleares, antifosfolípido y contra distintos antígenos de los neutrófilos, en ocasiones con un patrón característico. El estudio histológico suele mostrar cambios vasculares como vasculitis leucocitoclástica, necrosis de la pared y trombos. En este artículo revisamos las características clínicas, serológicas e histológicas de estas entidades, junto con los mecanismos fisiopatológicos implicados, el diagnóstico diferencial y su tratamiento. (AU)

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen.In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments. (AU)

[Translated article] Cutaneous and Mucosal Conditions Associated With Cocaine Use / Cuadros cutáneo-mucosos asociados al consumo de cocaína

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments. (AU)

El consumo de cocaína, junto con algunos de sus adulterantes más frecuentes como el levamisol, puede provocar múltiples procesos cutáneos y mucosos, ya sean de índole isquémico, dermatosis neutrofílicas, lesiones destructivas de la línea media y vasculitis asociadas a ANCA, entre otros. Generalmente no se asocia clínica sistémica llamativa. Todos estos cuadros pueden presentar anticuerpos antinucleares, antifosfolípido y contra distintos antígenos de los neutrófilos, en ocasiones con un patrón característico. El estudio histológico suele mostrar cambios vasculares, como vasculitis leucocitoclástica, necrosis de la pared y trombos. En este artículo revisamos las características clínicas, serológicas e histológicas de estas entidades, junto con los mecanismos fisiopatológicos implicados, el diagnóstico diferencial y su tratamiento. (AU)

Cutaneous and Mucosal Conditions Associated With Cocaine Use. / Cuadros cutáneo-mucosos asociados al consumo de cocaína.

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments.

Vasculitis inducida por cocaína-levamisol con manifestaciones cutáneas, articulares y abdominales: reporte de caso / Cocaine-levamisole induced vasculitis with cutaneous, joint and abdominal manifestations: case report

Resumen El levamisol es un antiparasitario de uso veterinario que actualmente es empleado para aumentar el volumen y la potencia de la cocaína. La mezcla de estas dos sustancias puede causar un cuadro caracterizado por lesiones propias de la cocaína, como la afección del cartílago septal con perforación del tabique nasal, y vasculitis cutánea de pequeños vasos con afectación de los pabellones auriculares y del cartílago nasal, afección conocida como vasculitis inducida por cocaína-levamisol (VICOL) que puede avanzar a necrosis e incluso ulceraciones cutáneas, asociadas a agranulocitosis, artralgias y glomerulonefritis . En el presente artículo se describe el caso de un paciente con historia de consumo de sustancias en quien se encontraron lesiones purpúricas palpables en miembros superiores, tronco, pabellones auriculares y miembros inferiores. Se consideró una clínica sugestiva de VICOL dado el antecedente de consumo de sustancias. En el proceso diagnóstico se descartaron entidades como la vasculitis por anticuerpos contra el citoplasma de los neutrófilos (ANCAs) y crioglobulinemia, entre otras posibles afecciones. Se llevó a cabo un tratamiento con esteroides y con ello presentó una respuesta adecuada, pero luego recurrieron los síntomas, particularmente abdominales, los cuales se consideraron asociados con vasculitis. Se le brindó manejo adicional con ciclofosfamida y nuevos pulsos de esteroides, con que se logró el control total de los síntomas. A través este caso se resaltan entonces los ejercicios diagnósticos y clínicos en la vasculitis cocaína- levamisol, y se sugiere la consideración de los síntomas abdominales como posible componente del cuadro vasculítico.

Abstract Levamisole is an antiparasitic agent for veterinary use. Currently it is used to increase the volume and potency of cocaine. Levamisole and cocaine combined result in the septum nasal perforation and small-vessel vasculitis in the ears and nasal cartilage. These findings are known as cocaine levamisole-induced vasculitis and can progress to necrosis and even skin ulceration, which is associated with agranulocytosis, arthralgia, and glomerulonephritis. This article describes the case of a patient with a history of substance abuse in whom palpable purpuric lesions were found in the upper and lower limbs, trunk, and ears. A clinical condition suggestive of vasculitis induced by cocaine-levamisole was considered, given the history of substance consumption. In the diagnostic process, entities such as Anti-neutrophil Cytoplasmic Antibodiy (ANCA) vasculitis and cryoglobulinemia, among other possible conditions, were ruled out. Steroid treatment was carried out, to which the patient had an adequate response, but then symptoms recurred, particularly abdominal, which were associated with vasculitis. Additional management with cyclophosphamide and new steroid pulses were provided, and with those symptom control was achieved. In this case report highlights the diagnostic and clinical exercises in cocaine levamisole vasculitis and is suggested the consideration of abdominal symptoms as a possible component of the vasculitis flare.

Necrosis auricular bilateral secundaria a cocaína adulterada con levamisol / Bilateral auricular necrosis secondary to levamisole-adulterated cocaine

La cocaína es la droga estimulante ilegal más consumida en Europa, siendo España uno de los países con mayor consumo. La adulteración de la cocaína con levamisol, de nueva aparición, ha provocado casos de neutropenia severa y vasculitis necrotizante. Presentamos el caso de un paciente que tras consumo de cocaína adulterada con levamisol presenta clínica sugestiva de necrosis bilateral de pabellón auricular. La adulteración de la cocaína con levamisol puede inducir una reacción inmunológica de tipo vasculitis causando necrosis cutánea irreversible si no cesa su uso. El tratamiento con aspirina y corticoides es aún controvertido. A pesar de ser una entidad rara, el conocimiento de este tipo de lesión es importante en nuestro medio para un precoz diagnóstico y tratamiento. (AU)

Cocaine is one of the most consumed ilegal drugs in Europe, with Spain heading the list. The recent appearance of levamisol-adulterated cocaine has led to new cases of severe neutropenia and necrotizing vasculitis among consumers. We report a case of a patient with bilateral auricular necrosis after levamisole-adulterated cocaine. Adulteration of cocaine with levamisole can lead to inmunological vasculitis-like response causing irreversible skin nerosis if continuosly consumed. Aspirin and corticotherapy treatment are still controversial. Although skin necrosis secondary to levamisole-adulterated cocaine is still unusual, diagnosis and early treatment of this kind of entity is crucial. (AU)

Vasculitis y vasculopatía con compromiso cutáneo, nasal y pulmonar inducida por consumo de cocaína-levamisol / Vasculitis and vasculopathy with cutaneous, nasal and pulmonary involvementinduced by cocaine-levamisole use

Resumen La cocaína pura y la contaminada con levamisol producen múltiples dermatosis, siendo las más frecuentes las lesiones destructivas de línea media y las vasculitis similares a las ANCA. Las bases fisiopatológicas de estas manifestaciones se sustentan en el daño vascular secundario a vasculitis y/o vasculopatía, originado por ambas sustancias y en muchos casos se puede encontrar solapamiento de las formas clínicas, lo que puede llevar a diagnósticos erróneos. Los patrones de positividad de los auto anticuerpos, el patrón de las lesiones cutáneas y el contexto social, serán claves en el abordaje y tratamiento adecuado de estos pacientes.

Abstract Pure cocaine and contaminated cocaine with levamisole produce multiple cutaneous and systemic manifestations, being midline destructive lesions and ANCA-like vasculitis the most frequent ones. The pathophysiological bases of these manifestations are based on secondary vascular damage to vasculitis and/or vasculopathy caused by both substances and in many cases it may be found an overlapping of the clinical forms, which might lead to erroneous diagnoses. The patterns of positivity of the autoantibodies, the pattern of skin lesions and the social context of the patient will be key in the proper approach and management of these patients. The following case describes a patient with cutaneous, nasal and pulmonary manifestations due to cocaine / levamisole consumption. Also, a review of the literature is carried out.

Glomerulonefritis crescéntica secundaria a consumo de cocaína adulterada con levamisol. Reporte de un caso y revisión de la literatura / Crescentic glomerulonephritis associated with levamisole-adulterated cocaine. A case report and a review of the literature

Resumen Introducción: El levamisol es un fármaco antihelmíntico, también conocido por su uso como inmunomodulador el cual, como consecuencia de sus efectos tóxicos, fue retirado a finales del siglo XX. En el 2005, producto de un incremento en el diagnóstico de vasculitis pauci-inmune entre la población usuaria de sustancias psicoactivas, se documentó la adulteración con fines comerciales de la cocaína combinándola con levamisol, a partir de un aumento de manifestaciones reumáticas asociadas al consumo de dicha droga. Reporte de caso: Se presenta el caso de un adulto joven con antecedentes de síndrome de Alport y consumo reciente de sustancias psicoactivas. Se realiza biopsia renal demostrándose la presencia de glomerulonefritis crescéntica pauci-inmune. Por lo anterior, se relacionó este tipo de vasculitis de pequeño vaso con afectación renal y depósito de complejos inmunes al consumo de cocaína adulterada con levamisol. Discusión: El levamisol, medicamento aprobado por la FDA en 1991, actúa como inmunomodulador, antiparasitario y coadyuvante en quimioterapia. El levamisol produce un síndrome reumático caracterizado por la presencia de glomerulonefritis, hemorragia alveolar, púrpura retiforme, neutropenia y agranulocitosis en relación con la presencia de anticuerpos anticitoplasma de neutrófilo. Conclusión: El levamisol es conocido por sus propiedades antihelmínticas e inmunomoduladoras, adicionalmente puede producir efectos tóxicos ostensibles. Dado el alto consumo de cocaína entre la población indigente, la presencia de este adulterante constituye un problema de salud pública creciente.

Abstract Introduction: Levamisole is an anthelmintic drug, also known for its use as an immunomodulator which, because of its toxic effects, was withdrawn at the end of the 20th century. In 2005, because of an increase in the diagnosis of pauci-immune vasculitis among the population that uses psychoactive substances, the adulteration of cocaine for commercial purposes by combining it with levamisole was documented. Case Report: The case of a young adult with a history of Alport Syndrome and recent consumption of psychoactive substances is presented. A renal biopsy is performed, demonstrating the presence of pauci-immune crescentic glomerulonephritis. Therefore, this type of small vessel vasculitis with kidney involvement and immune complex deposition was associated with the use of cocaine adulterated with levamisole. Discussion: Levamisole, a drug approved by the FDA in 1991, acts as an immunomodulator, antiparasitic and adjuvant in chemotherapy. Levamisole produces a rheumatic syndrome characterized by the presence of glomerulonephritis, alveolar hemorrhage, retinal purpura, neutropenia, and agranulocytosis in association with the presence of anti-neutrophil cytoplasmic antibodies. Conclusion: levamisole is known for its anthelmintic and immunomodulatory properties, additionally it can produce ostensible toxic effects. Given the high consumption of cocaine among the indigent population, the presence of this adulterant constitutes a growing public health problem.

Terapia com Levamisole em crianças e adolescentes com Síndrome Nefrótica Córtico dependentes ou recidivantes frequentes: experiência de um centro de referência em Minas Gerais / Levamisole therapy in dependent children and adolescents with Cortic Nephrotic Syndrome or frequent relapses: experience from a reference center in Minas Gerais

Introdução: A terapia poupadora de corticoide é a melhor estratégia para reduzir a exposição a esteroides a longo prazo em pacientes com síndrome nefrótica e o levamisole se mostrou um agente poupador de corticoide de baixo custo, fácil acesso e com baixo índice de eventos adversos. Objetivos: Sintetizar as evidências literárias sobre as estratégias poupadoras de corticoterapia em pacientes pediátricos com síndrome nefrótica. Avaliar a resposta ao uso de levamisole em pacientes pediátricos com síndrome nefrótica córtico dependentes ou recidivantes frequentes. Métodos: Revisão integrativa das evidências disponíveis na literatura em relação ao uso de poupadores de corticoide em pacientes pediátricos com síndrome nefrótica corticossensível recidivantes frequentes ou cortico dependentes. Levantamento de dados de pacientes em uso de levamisole para avaliação da resposta à medicação. Resultados: Não há uma medicação poupadora de corticoide de referência na população pediátrica. Quando necessária, a terapia poupadora de corticoterapia deve ser individualizada e compartilhada com familiares. O uso de corticoide continua sendo o tratamento inicial de escolha. Dos 30 pacientes selecionados para o estudo 86,7% não apresentaram efeitos adversos com uso de levamisole. O poupador de corticoide mais comumente utilizado antes do uso de levamisole foi a ciclofosfamida (26,7%). A biópsia renal foi realizada em 30% dos pacientes e o achado mais comum foi doença por lesões mínimas. Ao longo da avaliação em um ano, não houve piora de nenhum índice hematimétricos (P > 0,05) incluindo neutrófilos. Conclusões: Em nosso estudo o levamisole mostrou eficiência em reduzir o número de recidivas no primeiro ano de uso, além de manter estabilidade da função renal, com baixo índice de evento adverso.

Introduction: Corticosteroid-sparing therapy is the best strategy to reduce long-term steroid exposure in patients with nephrotic syndrome, and levamisole has been shown to be a low-cost, easily accessible, steroid-sparing agent with a low rate of adverse events. Objectives: To synthesize the literature evidence on steroid-sparing strategies in pediatric patients with nephrotic syndrome. To evaluate the response to the use of levamisole in pediatric patients with cortico-resistant nephrotic syndrome or frequent relapses. Methods: An integrative review of the evidence available in the literature regarding the use of steroid-sparing agents in pediatric patients with frequent relapsing or steroid-dependent cortico-sensitive nephrotic syndrome. Data collection of patients using levamisole to assess the response to medication. Results: There is no reference corticosteroid-sparing medication in the pediatric population. When necessary, steroid-sparing therapy should be individualized and shared with family members. Corticosteroid use remains the initial treatment of choice. Of the 30 patients selected for the study, 86.7% had no adverse effects with the use of levamisole. The most used corticosteroid sparing agent before the use of levamisole was cyclophosphamide (26.7%). Renal biopsy was performed in 30% of patients and the most common finding was focal segmental glomerulus sclerosis (FSGS), followed by minimal change disease. Over the course of the one-year evaluation, there was no worsening of any RBC index (P > 0.05) including neutrophils. Conclusions: In our study, levamisole showed efficiency in reducing the number of relapses in the first year of use, in addition to maintaining stability of renal function, with a low rate of adverse events.

Agranulocitosis febril y artropatía reactiva asociada a consumo de cocaína en un paciente HLA B27 positivo / Febrile agranulocytosis and reactive arthropathy associated with cocaine consumption in an HLA B27 positive patient

Resumen La agranulocitosis asociada al consumo de cocaína es un fenómeno vinculado a la presencia de levamisol, un agente antihelmíntico e inmunomodulador, usado como adulterante de la cocaína. Esta reacción puede presentarse con mayor frecuencia en personas con HLA B27. Además de la agranulocitosis, las personas que consumen cocaína adulterada con levamisol pueden desarrollar fiebre, lesiones en piel, artralgias y, menos frecuentemente, artritis y entesitis inflamatoria. Presentamos el caso de un paciente consumidor de cocaína, con genotipo HLA B27, que desarrolló agranulocitosis febril y artropatía reactiva. En sangre se detectó la presencia de ANCA p, ANCA atípico y MPO, y fueron excluidas otras causas de agranulocitosis. Fue tratado con corticoides y posteriormente metotrexato, terapia de deshabituación, con buena evolución.

Abstract Agranulocytosis associated with cocaine use is a phenomenon linked to the presence of levamisole, an anthelminthic and immunomodulating agent, used as an adulterant to cocaine. This reaction has been associated with the presence of HLA B27. In addition to agranulocytosis, people who use levamisole-adulterated cocaine may develop fever, skin lesions, arthralgias, and less frequently, inflammatory enthesitis and arthritis. We present the case of a cocaine-consuming patient with HLA B27 genotype, who developed febrile agranulocytosis and inflammatory arthropathy. The presence of p ANCA, atypical ANCA and MPO was detected in blood, and other causes of agranulocytosis were excluded. He was treated with corticosteroids and later methotrexate, therapy for addiction, with good evolution.

Pulmonary-renal syndrome secondary to cocaine-levamisole-induced vasculitis: A case report. / Síndrome pulmón-riñón secundario a vasculitis por cocaína/levamisol: reporte de caso.

Pulmonary-renal syndrome has rarely been reported as the clinical presentation of vasculitis caused by the consumption of cocaine adulterated with levamisole. We report the case of a patient in whom we detected the clinical manifestations and indicate the difficulties that arose in relation to the diagnostic and therapeutic approach.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control / Suscetibilidade in vitro de fungos nematófagos à antiparasitários: interações e implicações para o controle biológico

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animal's endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 μg/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 μg/mL para o levamisol, e entre 0,625 e 0,034 μg/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animals endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 g/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 g/mL para o levamisol, e entre 0,625 e 0,034 g/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

Cocaína adulterada con levamisol: reporte de tres casos clínicos / Levamisole-adulterated cocaine: a report on three clinical cases

El consumo de clorhidrato y pasta base de cocaína en Uruguay tiene una prevalencia de vida del 6,9% y 0,7% respectivamente. Las complicaciones tóxicas secundarias al consumo dependen de la concentración del alcaloide así como de la presencia de adulterantes. El levamisol, antihelmíntico veterinario, reconocido adulterante de la cocaína en Estados Unidos (2003), fue detectado en Uruguay en el año 2013. Este adulterante genera complicaciones tales como neutropenia, vasculitis cutánea, glomerulonefritis, hemorragia pulmonar y leucoencefalopatía. Se describen los tres primeros casos clínicos de complicaciones por levamisol como adulterante de cocaína reportados al Centro de Información y Asesoramiento Toxicológico. Los pacientes eran consumidores crónicos con edades entre los 35 y 40 años. En los tres casos se objetivó un púrpura retiforme con centro necrótico asociado a anticuerpos ANCA positivos con tendencia a presentarse en lóbulos de orejas, mejillas y extremidades, tal como se reporta en las vasculitis por levamisol. Se reportó neutropenia asociada en un caso. Los tres pacientes presentaron anemia. Dos casos presentaron falla renal aguda. El tratamiento principal fue el cese del consumo, lo que produjo una reversión completa de las complicaciones. Todos requirieron debridación o injertos de piel, o ambos. Se discuten y analizan las complicaciones mencionadas así como el riesgo que conlleva la reexposición y los tratamientos propuestos para las mismas, tales como los factores de crecimiento de granulocitos, antibióticos de amplio espectro y los corticoides. Se requiere un alto índice de sospecha para vincular estas manifestaciones clínicas a la presencia de levamisol como adulterante de la cocaína.

Consumption of cocaine hydrochloride and cocaine base paste (CBP) in Uruguay has a lifetime prevalence of 6.9% and 0.7% respectively. Complications associated to toxic side effects of cocaine abuse depend on the concentration of the alkaloid, as well as on the presence of adulterants. Levamisole, a veterinary anthelmintic, a well know cocaine adulterant in the US was identified in Uruguay in 2013. This adulterant results in complications such as neutropenia, skin vasculitis, glomerulonephritis and leukoencephalopathy. The study describes the first three clinical cases of complications resulting from cocaine cut with levamisole reported to the Toxicology Center for Information and Counseling. The patients included were chronic cocaine abusers between 35 and 40 years old. Retiform purpura was detected in the three cases with a necrotic center associated to ANCA antibodies, with a tendency to appear in the earlobes, cheeks, and limbs, as it is reported in levamisole associated vasculitis. Neutropenia was reported in one case. The three patients had anemia. Two of the cases presented acute kidney failure. The main treatment was interruption of consumption, what resulted in a complete reversion of complications. All patients required debridement or skin grafts, or both. The above mentioned complications are discussed and analyzed, as well as the risk re-exposure and the suggested treatments involve, as the granulocytes growth factors, broad spectrum antibiotics and corticoids. A high degree of suspicion is required to associate these clinical manifestations to the presence of levamisole as a cocaine adulterant.

O consumo de cloridrato e pasta base de cocaína no Uruguai tem uma prevalência de vida de 6,9% e 0,7% respectivamente. As complicações tóxicas secundarias ao consumo dependem da concentração do alcaloide como também da presença de adulterantes. O levamisol, anti-helmíntico veterinário, um conhecido adulterante da cocaína nos Estados Unidos (2003), foi detectado no Uruguai em 2013. Este adulterante gera complicações tais como neutropenia, vasculite cutânea, glomerulonefrite, hemorragia pulmonar e leucoencefalopatia. Os três primeiros casos clínicos de complicações por levamisol como adulterante de cocaína informados ao Centro de Información y Asesoramiento Toxicológico são descritos. Os pacientes eram consumidores crônicos com idades entre 35 e 40 anos. Nos três casos se observou púrpura retiforme com centro necrótico associado a anticorpos ANCA positivos com tendência a apresentação nos lóbulos das orelhas, bochechas e extremidades, como estão descritas nas vasculites por levamisol. Em um caso foi observada neutropenia. Três pacientes apresentaram anemia e dois falha renal aguda. O tratamento principal foi a cessação do consumo com reversão total das complicações. Foi necessário realizar debridação ou enxertos de pele, ou ambos em todos os casos. As complicações mencionadas bem como o risco vinculado à reposição e os tratamentos propostos para as mesmas, como por exemplo os fatores de crescimento de granulócitos, antibióticos de amplio espectro e corticoides, são discutidos e analisados. É necesssário um alto índice de suspeita para vincular estas manifestações clínicas à presença de levamisol como adulterante da cocaína.

[Cutaneous and mucosal manifestations associated with cocaine use]. / Manifestaciones cutáneas y mucosas asociadas al consumo de cocaína.

Complications due to cocaine are a public health problem. The typical cutaneous disease is leukocytoclastic vasculitis and/or thrombotic vasculopathy affecting mainly the ears. No intense systemic involvement is usually present, but there may be several cutaneous, mucosal and systemic manifestations. Other findings associated as arthralgia, neutropaenia or agranulocytosis, low titer positive antinuclear antibodies, antiphospholipid antibody positivity and neutrophil cytoplasmic antibodies against multiple antigens help the diagnosis. This disease requires a clinical suspicion with a clinical history, a complete physical examination and a broad differential diagnosis for an early and correct diagnosis. The course is usually self-limited. In most cases the only treatment is to discontinue the use of cocaine associated with symptomatic treatment, no proven benefit of systemic corticosteroids.

3 cases of cocaine - levamisole syndrome in Medellín / Presentación de tres casos de síndrome cocaína - levamisol en Medellín

El levamisol es un antihelmíntico de uso veterinario que ha sido utilizado como aditivo a la cocaína con el objetivo de aumentar los efectos psicotrópicos de dicha sustancia. Esta mezcla produce reacciones como agranulocitosis, vasculitis cutánea y modulación del sistema inmune. Solamente el reconocimiento, tratamiento adecuado y la suspensión del consumo de esta sustancia lleva a la desaparición de las lesiones y sugiere fuertemente el diagnóstico. Presentamos tres casos de síndrome cocaína/levamisol en Medellín y una revisión de la literatura con algunos conceptos de esta enfermedad.

Levamisole, an anthelmintic veterinary product is known to be used as an additive to cocaine that enhances the psychotropic effects of this substance. This mixture leads to reactions such as agranulocytosis, skin vasculitis and modulation of the immune system. Only the proper recognition, treatment of this entity and discontinuation of this substance consumption, leads to the disappearance of lesions; strongly suggesting the diagnosis. We present three cases of cocaine/levamisole syndrome in the city of Medellin and a review of the literature with some concepts related to this pathology.

Agranulocitosis por levamisol asociado a cocaína / Agranulocytosis induced by levamisole in association to cocaine

La neutropenia en usuarios de cocaína es una condición de reciente reconocimiento en distintos países. Se debe a la utilización del levamisol, una antigua droga antiparasitaria e inmunomoduladora, como agente de corte. Presentamos el caso de un paciente con agranulocitosis por levamisol asociado a cocaína y una revisión de las características del cuadro, así como del control de estos pacientes. También se tratan los motivos vinculados al agregado cada vez más frecuente de levamisol a la cocaína. Este es el primer caso descrito en nuestro país, si bien es probable que existan muchos casos no reconocidos o no comunicados de esta enfermedad.

Agranulocytosis in cocaine users is a worldwide recently recognized condition. It is due to the utilization as cutting agent of levamisole, an ancient antiparasitic and immunomodulator drug. We describe the case of a patient with agranulocytosis induced by levamisole in association to cocaine and we review clinical and biochemical characteristics of the clinical picture, as well as the management of these patients. We also analyze the reasons related to a more and more frequent practice, the addition of levamisole to cocaine. This is the first case described in our country, although it is probable that there are many not recognized or not described cases related to this pathology.

Agranulocitosis por levamisol asociado a cocaína / Agranulocytosis induced by levamisole in association to cocaine

La neutropenia en usuarios de cocaína es una condición de reciente reconocimiento en distintos países. Se debe a la utilización del levamisol, una antigua droga antiparasitaria e inmunomoduladora, como agente de corte. Presentamos el caso de un paciente con agranulocitosis por levamisol asociado a cocaína y una revisión de las características del cuadro, así como del control de estos pacientes. También se tratan los motivos vinculados al agregado cada vez más frecuente de levamisol a la cocaína. Este es el primer caso descrito en nuestro país, si bien es probable que existan muchos casos no reconocidos o no comunicados de esta enfermedad.(AU)

Agranulocytosis in cocaine users is a worldwide recently recognized condition. It is due to the utilization as cutting agent of levamisole, an ancient antiparasitic and immunomodulator drug. We describe the case of a patient with agranulocytosis induced by levamisole in association to cocaine and we review clinical and biochemical characteristics of the clinical picture, as well as the management of these patients. We also analyze the reasons related to a more and more frequent practice, the addition of levamisole to cocaine. This is the first case described in our country, although it is probable that there are many not recognized or not described cases related to this pathology.(AU)

Vasculitis cutánea leucocitoclástica y glomeruesclerosis focal y segmentaria con formación de semi lunas en una joven consumidora de cocaína/crack cortada con levamisol V / Cutaneous leukocytoclastic vasculitis and focal segmental glomeruesclerosis with crescent formation in a young consumer of cocaine / crack cut with levamisole V

Se describen los hallazgos anatomopatológicos encontrados en la autopsia de una joven de 19 años de edad, indigente, trabajadora del sexo, adicta al crack desde los 12 años de edad, quien los últimos 4 meses de su vida tuvo tres ingresos hospitalarios al Hospital México de San José‚ de Costa Rica con diagnóstico de vasculitis cutánea por crack e insuficiencia renal aguda. Los hallazgos más relevantes en la autopsia fueron: vasculitis aguda leucocitoclástica con trombosis y paniculitis glomeruloesclerosis focal y segmentaria con formación de semilunas...

Diagnóstico do controle e perfil de sensibilidade de nematódeos de ovinos ao albendazol e ao levamisol no norte de Minas Gerais / Diagnostic of the control and sensitivity profile of nematodes from sheep to albendazole and levamisole in northern Minas Gerais, Brazil

A resistência anti-helmíntica é um dos principais entraves para o controle da verminose em ruminantes e a presença de nematódeos multiresistentes pode inviabilizar a atividade em uma determinada área. Neste trabalho o objetivo foi avaliar a eficácia anti-helmíntica do levamisol e do albendazol em rebanhos ovinos do norte de Minas Gerais. O teste foi realizado em dez propriedades, onde foram selecionados três grupos de 12 borregos cada. Dois desses grupos foram tratados respectivamente com levamisol (5 mg/kg pc) ou albendazol (10 mg/kg pc) e o terceiro grupo não foi tratado. Fezes foram coletadas antes do tratamento e no sétimo dia após, para a realização do teste de redução de ovos por grama de fezes. Foi realizado o cultivo de larvas provenientes dos grupos avaliados para a identificação dos principais gêneros de nematódeos gastrintestinais antes e após os tratamentos. Para todos os rebanhos avaliados no norte de Minas Gerais, o levamisol apresentou eficácia anti-helmíntica elevada, variando de 90% a 100%. Apenas para um rebanho o albendazol seria efetivo e para seis propriedades as eficácias dessa droga foram inferiores a 80%, sendo considerada insuficientemente ativa. Após as coproculturas foram identificadas, em maior ocorrência, larvas dos gêneros Haemonchus e Trichostrongylus. O gênero Haemonchus foi o mais prevalente mesmo após o tratamento dos ovinos. Ressalta-se neste estudo a importância do teste de eficácia in vivo para a escolha das bases anti-helmínticas nas propriedades, pois foi observado que o perfil de susceptibilidade variou entre os diferentes rebanhos.

The anthelmintic resistance is a major obstacle for the nematode control in ruminants and the presence of multiresistant nematodes could make impracticable the activity in a given area. The objective in this study was to evaluate the anthelmintic efficacy of albendazole and levamisole in sheep herds in northern Minas Gerais. The test was performed on ten farms, where we selected three groups of 12 lambs each. Two of these groups were respectively treated with levamisole (5mg/kg) or albendazole (10mg/kg). The third group did not receive treatment. Feces were collected at 0 and 7 day after treatment for the fecal egg reduction test. The nematode genus was evaluated with the identification of the larvae obtained from culture in the feces pre- and post-treatments. For all evaluated herds the levamisole showed high anthelminthic efficacy, which ranged from 90 to 100%. Only for one herd, the albendazole was effective and for six farms, the efficacy of this drug was less than 80%, considered insufficiently active. After the cultivation of larvae were identified mainly Haemonchus spp. and Trichostrongylus spp. The genus Haemonchus was the most prevalent even after treatment of sheep. It is emphasized the importance of in vivo efficacy tests for choosing anthelmintic drugs, since the susceptibility profile varied among sheep herds evaluated in this study.

Tratamiento del síndrome nefrótico idiopático / Treatment of the idiopathic nephrotic syndrome

A pesar de los años transcurridos desde la descripción del síndrome nefrótico, del desarrollo de la industria farmacéutica y de los medicamentos con que se cuenta para enfrentar esta glomerulopatía, todavía existen pacientes de muy difícil tratamiento, que obligan a utilizar diferentes fármacos sin que se pueda asegurar con exactitud la respuesta en cada caso. Los pacientes que no responden a los esteroides constituyen un grupo especial y de difícil control, pero los que presentan recaídas frecuentes o corticodependencia también obligan en muchas ocasiones al empleo de otros medicamentos con toxicidad especial y respuesta no precisa. Por tal motivo se considera de interés esta revisión sobre los fármacos que con mayor frecuencia se pueden utilizar y sobre la indicación de cada uno de ellos. Sin pretender agotar el tema, se trata de llevar al pediatra una posible guía para el tratamiento de los casos de difícil control.

Despite the years passed from the description of nephrotic syndrome, the development of pharmaceutical industry and of the drugs available to face this glomerulopathy, still there are patients very difficult to treat, who oblige us to use different drugs without achieve exactly the response in each case. Patients non-respondent to steroids are a special group and of difficult control, but those having frequent relapses or cortico-dependent also oblige us to use another drugs with a special toxicity and non-precise response. Thus, this is considered an interesting review on drugs more frequent used and on prescription of each of them. Without exhaust the subject, we try to offer the pediatricians a possible guide for treatment of cases of difficult control.