Síndrome urémico hemolítico del adulto / Adult hemolytic uremic syndrome

El síndrome urémico hemolítico (SUH), descripto en 1955, se caracteriza por la tríada de anemia hemolítica no inmunomediada, trombocitopenia y lesión renal aguda. En su patogenia interviene la toxina Shiga, producida con mayor frecuencia por E. coli O157:H. Puede manifestarse a cualquier edad, aunque es infrecuente en adultos, y se desarrolla en forma esporádica o en brote. Se presenta con un cuadro de dolor abdominal, diarrea, fiebre y vómitos. Puede afectar el sistema nervioso central, pulmones, páncreas y corazón. En adultos, el síndrome evoluciona tras un período de incubación de 1 semana posterior a la diarrea y tiene alta morbimortalidad, a diferencia de los casos pediátricos. Presentamos el caso de una paciente adulta, que cursó internación por síndrome urémico hemolítico. (AU)

Hemolytic uremic syndrome (HUS), described in 1955, is characterized by the triad of non-immune mediated hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin, produced most frequently by E coli O157:H, is involved in its pathogenesis. Hus can manifest at any age, although it is rare in adults and develops sporadically or in outbreaks. HUS presents with a picture of abdominal pain, diarrhea, fever and vomiting. It can affect the central nervous system, lungs, pancreas, and heart.In adults, the syndrome evolves after an incubation period of 1 week after diarrhea, with high morbidity and mortality, unlike pediatric cases.We present the case of an adult patient who was hospitalized for hemolytic uremic syndrome. (AU)

Síndrome urémico hemolítico: reporte de dos casos pediátricos con nexo epidemiológico / Hemolytic uremic syndrome: report of two pediatric clinical cases with epidemiologic link / Síndrome urémico hemolítico: reporte de casos pediátricos con nexo epidemiológico

Introducción: el síndrome hemolítico urémico (SHU) es en muchos países, de las causas más frecuentes de insuficiencia renal aguda. La mayoría de los casos ocurre luego de un episodio de gastroenteritis aguda (GEA) por Escherichia coli productora de toxina Shiga (STEC). En Uruguay a pesar de ser una enfermedad de notificación obligatoria, existe subregistro. Objetivo: describir dos casos clínicos de SHU asociados a GEA con nexo epidemiológico. Casos clínicos: se trata de dos varones de 4 y 5 años, sanos. En los días previos, ingesta de carne en el mismo local comercial. Consultaron por dolor abdominal, deposiciones líquidas y vómitos reiterados. El niño de 4 años presentaba fiebre y deposiciones líquidas con sangre. El niño de 5 años dolor abdominal. El estado de hidratación y las constantes vitales eran normales en ambos. Fueron admitidos a cuidados moderados. A las 48 horas y a los 5 días, respectivamente, agregan palidez cutáneo-mucosa intensa, edemas y oliguria. Estudios complementarios: anemia, plaquetopenia e insuficiencia renal. Ingresaron a cuidados intensivos y se realizó diálisis peritoneal. La investigación de STEC fue negativa y la evolución favorable. Conclusiones: en menores de 5 años el SHU asociado a GEA es la forma de enfermedad más frecuente. En Uruguay predominan las cepas STEC no-O157. En estos casos no se pudo identificar el agente. La existencia de un nexo epidemiológico alerta sobre la necesidad de extremar los cuidados en la preparación y cocción de la carne. Debido a la asociación con una enfermedad prevalente, es necesario tener presente esta complicación para poder sospecharla e iniciar el tratamiento en forma precoz y oportuna.

Introduction: hemolytic uremic syndrome (HUS) is one of the most frequent causes of acute renal failure in many countries. Most cases occur after an episode of acute gastroenteritis (GEA) due to the Shiga toxin producing Escherichia Soli (STEC). In Uruguay, despite being a disease that requires mandatory notification, it is under reported. Objective: to describe two clinical cases of HUS associated with GEA with an epidemiological link. Clinical cases: these are two healthy boys aged 4 and 5 years. In the previous days, they reported meat intake in the same commercial premises. They consulted for abdominal pain, liquid stools and repeated vomiting. The 4 year old boy had a fever and bloody stools. The 5 year old boy had abdominal pain. They both showed normal hydration levels and vital signs. They were admitted to moderate care. At 48 hours and 5 days, respectively, they showed intense skin and mucosal paleness, edema and oliguria. Complementary studies: anemia, thrombocytopenia and renal failure. They were admitted to intensive care and peritoneal dialysis was performed. The STEC's investigation was negative and the evolution favorable. Conclusions: in children under 5 years of age, HUS associated with GEA is the most frequent form of the disease. In Uruguay, non-O157 STEC strains predominate. In these cases, the agent could not be identified. The existence of an epidemiological link warns us about the need for extreme care in the preparation and cooking of meat. Due to the association with a prevalent disease, it is necessary to keep this complication in mind in order to suspect it and initiate early and timely treatment.

Introdução: a síndrome hemolítico urêmica (SHU) é uma das causas mais frequentes de insuficiência renal aguda em muitos países. A maioria dos casos ocorre após um episódio de gastroenterite aguda (GEA) devido à Escherichia Coli, a toxina produtora de Shiga (STEC). No Uruguai, apesar de ser uma doença de notificação compulsória, há subnotificação. Objetivo: descrever dois casos clínicos de SHU associada à AGE com vínculo epidemiológico. Casos clínicos: dois meninos saudáveis com idades entre 4 e 5 anos. Nos dias anteriores, eles reportaram consumo de carne nos mesmos estabe- lecimentos comerciais. Eles consultaram para dor abdominal, fezes líquidas e vômitos repetidos. O menino de 4 anos teve febre e fezes com sangue. O menino de 5 anos teve dores abdominais. O estado de hidratação e os sinais vitais foram normais em ambos meninos. Foram internados em cuidados moderados. Às 48 horas e 5 dias, respectivamente, apresentaram aliás palidez intensa da pele e mucosas, edema e oligúria. Realizaramse estudos complementares: anemia, trombocitopenia e insuficiência renal. Eles foram internados em terapia intensiva e realizouse diálise peritoneal. A investigação do STEC foi negativa e a evolução favorável. Conclusões: em crianças menores de 5 anos, a SHU associada à GEA é a forma mais frequente da doença. No Uruguai, predominam cepas STEC não-O157. Nesses casos, o agente não pôde ser identificado. A existência de um nexo epidemiológico alerta para a necessidade de extremo cuidado no preparo e cozimento da carne. Devido à associação com doença prevalente, é necessário considerar essa complicação para suspeitar e iniciar o tratamento precoce e oportunamente.

Vigilancia de síndrome urémico hemolítico / Surveillance of hemolytic uremic syndrome

Se presenta de manera breve la situación de Síndrome Urémico Hemolítico hasta la Semana Epidemiológica 15 de 2022, según datos de la notificación al Sistema Nacional de Vigilancia Epidemiológica, Incluye datos de notificación de agentes etiológicos 2021-2022.

Research Advances on the Pathogenesis and Treatment of Hemolytic Uremic Syndrome --Review / 中国实验血液学杂志

Hemolytic uremic syndrome (HUS) is clinically rare, with high mortality and case fatality rates. In recent years, the research on HUS has been intensified and the pathophysiological mechanism has been continuously improved. At present, the main mechanism of pathogenesis is the excessive activation of complement alternative pathways mediated by complement-related gene mutations or the existence of antibodies. The treatment methods and strategies are also constantly updated, mainly including complement-blocking drugs such as Eculizumab, Lavalizumab, and Ravulizumab. In this review, the new developments in the pathogenesis and treatment of HUS is summarized, and provide references for the clinical treatment of HUS.

Sensibilidad diagnóstica de la ampliación de los criterios hematológicos y renales para la definición de síndrome urémico hemolítico / Diagnostic sensitivity of extended renal and hematologic criteria to define hemolytic uremic syndrome

Introducción. La definición habitual de síndrome urémico hemolítico causado por Escherichia coli productora de toxina Shiga (STEC-SUH) se basa en la presencia de anemia, plaquetopenia y elevación de los niveles séricos de creatinina, acompañadas o no de proteinuria y/o hematuria. La definición estricta solo acepta como criterio renal el aumento de la creatinina sérica. La definición amplia mantiene criterios renales flexibles, aunque reemplaza la anemia por hemólisis y acepta la caída brusca del recuento plaquetario como indicador de consumo plaquetario. El objetivo de este estudio fue estimar y comparar la sensibilidad diagnóstica de dichas definiciones en pacientes con STEC-SUH como diagnóstico de egreso hospitalario. Población y métodos. Revisión retrospectiva de las historias clínicas de pacientes con SUH. Se calculó la sensibilidad y el valor predictivo positivo con sus intervalos de confianza 95 % (IC95 %) de las tres definiciones en función del diagnóstico de egreso de STEC-SUH (diagnóstico de referencia). Se utilizó la prueba de McNemar. Resultados. De 208 pacientes, 107 (51,4 %) fueron identificados con la definición estricta, 133 (63,9 %) con la habitual; y 199, con la amplia (95,6 %). La sensibilidad resultó menor para la definición estricta (51,4 %; IC 95 %: 44,8-58,3), intermedia para la habitual (63,9 %; IC 95 %: 56,9-70,4) y mayor para la amplia (95,6 %; IC 95 %: 91,6-97,8); (p < 0,001). Conclusión. Las distintas definiciones de STEC-SUH presentaron diferencias significativas en la sensibilidad diagnóstica. Dado que la definición amplia alcanzó una sensibilidad superior al 95 %, su uso generalizado podría disminuir la demora diagnóstica

Introduction. The usual definition of Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is based on the presence of anemia, thrombocytopenia, and elevated serum creatinine levels, with or without proteinuria and/or hematuria. The strict definition only considers elevated serum creatinine levels as a renal criterion. The extended definition maintains flexible renal criteria, although it replaces anemia with hemolysis and considers a sharp drop in platelet count as an indicator of platelet consumption. The objective of this study was to estimate and compare the diagnostic sensitivity of these definitions in patients with STEC-HUS as hospital discharge diagnosis. Population and methods. Retrospective review of medical records of HUS patients. Sensitivity and positive predictive value, with their corresponding 95 % confidence intervals (CIs), were estimated for the 3 definitions based on a discharge diagnosis of STEC-HUS (reference diagnosis). The McNemar test was used. Results. Out of 208 patients, 107 (51.4 %), 133 (63.9 %), and 199 (95.6 %) were identified with the strict, usual, and extended definition, respectively. Sensitivity was lower for the strict definition (51.4 %; 95 % CI: 44.8-58.3), intermediate for the usual definition (63.9 %; 95 % CI: 56.9-70.4), and higher for the extended one (95.6 %; 95 % CI: 91.6-97.8); (p < 0.001). Conclusion. The different STEC-HUS definitions showed significant differences in diagnostic sensitivity. The extended definition reached a sensitivity above 95 %, so its generalized use may help to reduce diagnostic delays

Tiempo de excreción fecal de Escherichia coliproductora de toxina Shiga en niños con síndrome urémico hemolítico / Duration of fecal shedding of Shiga toxin-producing Escherichia coli among children with hemolytic uremic syndrome

Introducción. Conocer el tiempo de excreción fecal de Escherichia coli productora de toxina Shiga (Shiga toxin-producing Escherichia coli; STEC, por sus siglas en inglés) en pacientes con síndrome urémico hemolítico sería útil para controlar la transmisión de la enfermedad.Objetivos. 1) Analizar las características del tiempo de excreción de STEC. 2) Evaluar la asociación con las variables sexo, edad, necesidad de diálisis, antibióticos y serotipos de STEC.Población y métodos. Estudio prospectivo, observacional, longitudinal y analítico. Período 2013-2019. Se realizaron coprocultivos al ingresar y cada 5-7 días hasta obtener 2 negativos. Se definió tiempo de excreción desde el inicio de la diarrea hasta el primer negativo. Se confirmó STEC por detección de los genes stx1, stx2 y rfbO157 por reacción en cadena de la polimerasa. Se calculó la media (IC 95 %) y percentilos del tiempo de excreción de STEC, y se compararon las variables estudiadas mediante el test de t.Resultados. Se incluyeron 43 pacientes. La media de tiempo de excreción fue 10,2 días (IC 95 %: 8,92-11,59), rango: 3-22 días. El 90 % de los pacientes negativizaron el coprocultivo a los 15 días. No hubo diferencias según sexo (p = 0,419), edad (p = 0,937), necesidad de diálisis (p = 0,917), antibióticos (p = 0,147) ni serotipos (p = 0,231).Conclusión. El 90 % de los pacientes negativizó el coprocultivo a los 15 días del inicio de la diarrea, y todos, al día 22. No se encontró asociación entre el tiempo de excreción y las variables estudiadas.

Introduction. Knowing the duration of fecal shedding of Shiga toxin-producing Escherichia coli(STEC) among patients with hemolytic uremic syndrome would be useful to control disease transmission.Objectives. 1) To analyze the characteristics of STEC shedding duration. 2) To assess the association with sex, age, need of dialysis, antibiotics, and STEC serotypes.Population and methods. Prospective, observational, longitudinal, and analytical study in the 2013-2019 period. Stool cultures were done upon admission and every 5-7 days until 2 negative results were obtained. Shedding duration was defined as the period from diarrhea onset to the first negative result. STEC was confirmed with polymerase chain reaction detection of stx1, stx2, and rfbO157 genes. The mean (95 % CI) and percentile values of the STEC shedding duration were estimated, and the studied outcome measures were compared using the t test.Results. A total of 43 patients were included. The mean duration of shedding was 10.2 days (95 % CI: 8.92-11.59), range: 3-22 days. After 15 days, 90 % of patients had a negative stool culture. There were no differences in terms of sex (p = 0.419), age (p = 0.937), need of dialysis (p = 0.917), antibiotics (p = 0.147) or serotype (p = 0.231).Conclusion. Fifteen days after the onset of diarrhea, 90 % of patients had a negative stool culture, and all patients had one after 22 days. No association was observed between the duration of shedding and studied outcome measures.

Hidratación en el síndrome urémico hemolítico / Hydration in hemolytic uremic syndrome

El síndrome urémico hemolítico asociado a diarrea es precedido por una gastroenteritis por Escherichia coli productora de toxina Shiga. Se recomiendan medidas de sostén, especialmente, la restricción hídrica para evitar la sobrecarga cardiopulmonar. Sin embargo, la expansión de volumen con líquidos isotónicos, en el período prodrómico o síndrome urémico hemolítico establecido, es segura y eficaz, reduce los requerimientos de diálisis, los días de internación y de terapia intensiva, los eventos neurológicos y la hiponatremia.Por ello, se propone, bajo supervisión nefrológica y/o garantizando el acceso a un centro de alta complejidad a corto plazo, hidratar a todo paciente sin signos de sobrecarga cardiopulmonar, independientemente de su función renal, con expansión inicial de volumen. Luego, si se logra una diuresis adecuada, no dializarlo (excepto que presente un trastorno metabólico/electrolítico intratable médicamente) y continuar la hidratación con una solución isotónica de dextrosa al 5 % para una adecuada hidratación y diuresis.

Diarrhea-associated hemolytic uremic syndrome is preceded by gastroenteritis due to Shiga toxin-producing Escherichia coli. Support measures are recommended, specifically, fluid restriction to avoid cardiopulmonary overload. However, in the prodromal period or with established hemolytic uremic syndrome, volume expansion with isotonic fluids is safe and effective, and reduces the need for dialysis, the length of hospital and intensive care stay, neurological events, and hyponatremia.Therefore, when nephrological monitoring is available and/or short-term access to a tertiary care hospital is guaranteed, it is suggested to hydrate patients with no signs of cardiopulmonary overload, regardless of their renal function, with initial volume expansion. Afterwards, if an adequate urine output is achieved, the patient should not be dialyzed (except if they have a medically intractable metabolic/electrolyte disorder) and hydration should be continued with an isotonic solution containing 5 % dextrose for adequate hydration and urine output.

Microangiopatías trombóticas primarias: una revisión narrativa / Primary thrombotic microangiopathies: a narrative review

La microangiopatía trombótica (MAT) es un síndrome donde hay formación de microtrombos en la circulación que llevan a anemia hemolítica microangiopática (AHMA) y trombocitopenia con falla multiorgánica, debido a la isquemia de los tejidos. Las MAT pueden ser primarias sin causa subyacente asociada, como la púrpura trombocitopénica trombótica debida a deficiencia de la enzima ADAMTS13, el síndrome hemolítico urémico debido a la toxina Shiga de Escherichia coli enterohemorrágica, y la MAT producida por alteraciones en la regulación del complemento. Adicionalmente, pueden ser secundarias a enfermedades malignas, infecciosas, metabólicas, autoinmunes o inducidas por el embarazo. Estas patologías requieren diagnóstico y tratamiento oportunos debido a que tienen alta morbimortalidad y se asocian a complicaciones que incluyen enfermedad renal, alteraciones neurológicas como convulsiones, accidente cerebrovascular, coma y muerte. El tratamiento es multidisciplinario y se enfoca en el soporte hemodinámico, transfusional y en el manejo de la etiología cuando esta es identificada. La siguiente revisión pretende explicar de forma clara y precisa los aspectos generales de las MAT primarias

Thrombotic microangiopathy (TMA) is a syndrome characterized by the formation of microthrombi in the circulation leading to microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, with multiorgan failure due to tissue ischemia. TMA can be primary with no associated underlying cause, such as thrombotic thrombocytopenic purpura due to ADAMTS13 deficiency, hemolytic uremic syndrome due to the Shiga toxin from enterohemorrhagic Escherichia coli, or due to complement dysregulation. Furthermore, TMA can be secondary to malignant, infectious, metabolic or autoimmune diseases, or induced by pregnancy. These conditions require a timely diagnosis and treatment due to their associated high morbidity and mortality, and complications like renal disease, neurological disorders such as seizures, stroke, coma and death. Treatment is multidisciplinary and focuses on hemodynamic and transfusion support, and on the management of the etiology when it is identified (daily plasma exchange, eculizumab or management of underlying disease). This review aims to discuss the general aspects of primary thrombotic microangiopathies

Síndrome hemolítico urémico en una mujer adulta mayor: reporte de caso y revisión de la literatura / Hemolytic uremic syndrome in an older adult woman: case report and literature review

El síndrome hemolítico urémico (SHU) típico en adultos es una patología infrecuente. En la literatura se encuentran pocos reportes, y se ha documentado principalmente en la población pediátrica. Esta entidad se caracteriza por ser una microangiopatía trombótica (MAT) que compromete de manera característica los riñones. Es causada usualmente por la infección por Escherichia coli productora de toxina Shiga (STEC), específicamente el serotipo O157:H7. En Colombia no existen casos reportados sobre esta condición en adultos, lo cual llama la atención, pero puede deberse en parte a las dificultades en su diagnóstico, al no tenerse fácil acceso a algunas de las pruebas que orientan hacia esta enfermedad y confirman el diagnóstico. Se reporta el caso de una mujer adulta mayor colombiana, quien consultó por deposiciones diarreicas y hematoquecia, con el posterior desarrollo de trombocitopenia severa, lesión renal aguda, y evidencia de equinocitos y esquistocitos en extendido de sangre periférica, lo que llevó a sospechar una MAT. Se le solicitó FilmArray® gastrointestinal, el cual fue positivo para STEC, confirmando así el diagnóstico de un SHU típico. Se presenta también una breve revisión del tema de una entidad que requiere un diagnóstico temprano y certero que permita brindar un tratamiento eficaz y oportuno

The classic or typical hemolytic uremic syndrome (HUS) in adults is a rare disease. Few reports are found in the literature, and it has mainly been documented in the pediatric population. This condition is a form of thrombotic microangiopathy (TMA), which characteristically compromises the kidneys. It is mainly caused by infection with Shiga toxin-producing Escherichia coli (STEC), specifically the O157:H7 serotype. In Colombia there are no reports on this condition in adults, and may be due in part to difficulties in its diagnosis, as there is not easy access to some of the tests that guide towards this condition and confirm the diagnosis. The case of an elderly Colombian woman is reported, who presented diarrhea and hematochezia, and subsequently developed severe thrombocytopenia and acute kidney injury, with evidence of echinocytes and schistocytes in peripheral blood smears, which led to suspect TMA. A gastrointestinal FilmArray™ was ordered, which was positive for STEC, thus confirming the diagnosis of a typical HUS. A brief literature review is also presented, which covers general concepts of a condition that requires an early and accurate diagnosis in order to provide an effective and timely treatment

Síndrome hemolítico urémico por ingesta de veneno de una serpiente del género Bothrops: Reporte de un caso / Hemolytic uremic syndrome due to ingestion of venom from a snake of the genus Bothrops: Report of a case

Resumen El síndrome hemolítico urémico (SHU) es una enfermedad que se caracteriza por la tríada anemia hemolítica no inmune, trombocitopenia e insuficiencia renal aguda, en la que las lesiones subyacentes están mediadas por un proceso de microangiopatía trombótica (MAT) sistêmica. Existen distintas causas que pueden desencadenar el proceso de la MAT que caracteriza el SHU. Se describe el caso de una mujer, con antecedentes de diabetes mellitus e hipertensión arterial, quién ingirió veneno de serpiente del género Bothrops con fines medicinales y 72 horas después debió ser hospitalizada por edema de miembros inferiores, dolor abdominal, equimosis e ictericia. Al ingreso, se le realizó analítica sanguínea que constató trombocitopenia, elevación de azoados y anemia; de igual forma se documentaron datos de falla renal aguda, por lo que se diagnosticó con SHU secundario a la ingesta de veneno de serpiente. En el artículo se describen aspectos del diagnóstico y el manejo clínico que se realizó y se estable que el compromiso renal por veneno de serpiente Bothrops es una entidad poco frecuente que si no se maneja de manera adecuada puede ser letal, y más aún si existen comorbilidades predisponentes.

Abstract Hemolytic uremic syndrome (HUS) is a disease characterized by the triad of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by a process of systemic thrombotic microangiopathy (TMA). There are different causes that can trigger the MAT process that characterizes HUS. The case of a woman with a history of diabetes mellitus and arterial hypertension is described, who ingested snake venom of the genus Bothrops for medicinal purposes, and 72 hours later she had to be hospitalized for edema of the lower limbs, abdominal pain, ecchymosis and jaundice. Upon admission, he underwent blood tests that found thrombocytopenia, elevated nitrogen levels and anemia; Similarly, data on acute kidney failure were documented, for which HUS was diagnosed secondary to the ingestion of snake venom. The article describes aspects of the diagnosis, and the clinical management that was carried out and it was established that renal involvement by Bothrops snake venom is a rare entity, which if not managed properly can be lethal, and even more so if there are predisposing comorbidities.

Eculizumab como opción terapéutica en paciente con crisis renal esclerodérmica asociada a síndrome hemolítico urémico / Eculizumab as a therapeutic option in patients with scleroderma renal crisis associated with haemolytic uraemic syndrome

RESUMEN La crisis renal esclerodérmica (CRS) es una manifestación rara de la esclerosis sistémica (ES). Se presenta como hipertensión arterial de nuevo inicio, empeoramiento o aceleración de la hipertensión arterial crónica o rápido deterioro de la función renal, frecuentemente acompañada de signos de hemolisis microangiopática. Su relación con el síndrome hemo lítico urémico es infrecuente, existiendo tan solo un caso similar reportado en la literatura. Presentamos el caso de una mujer de 36 arios en tratamiento para ES con cefalea global, pulsátil e intensa, convulsión tónico-clónica, cifras de presión arterial altas, falla renal aguda y hemólisis no autoinmune persistente. La evaluación de ADAMTS13 mostró un 60,6% de actividad. El estudio genético para búsqueda de mutaciones predisponentes para sín drome hemolítico urémico atípico (SHUa) reveló variante homocigota en el gen ADAMTS13, c.3287G>A (p.Arg1096His). Se inició tratamiento con eculizumab, observándose en poco tiempo mejoría de la hemólisis, función renal y estado clínico, con algunos efectos benéficos notorios e inesperados sobre la ES.

ABSTRACT Scleroderma renal crisis (SRC) is a rare manifestation of systemic sclerosis (SSc), presented as hypertension of new onset, worsening and / or acceleration of chronic hypertension, or rapid deterioration of renal function, often accompanied by signs of microangiopathic haemolysis. It is rarely associated with haemolytic uraemic syndrome, and there is only one similar case reported in the literature. The case is presented here of a 36-year-old woman on treatment for SSc with global, pulsatile and intense headache, clonic tonic convulsions, high blood pressure levels, acute renal failure, and persistent non-autoimmune haemoly sis. The evaluation of ADAMTS13 showed 60.6% of activity. The genetic study to search for mutations predisposing to atypical haemolytic uraemic syndrome (aHUS) revealed a homozygous variant in ADAMTS13 gene, c.3287G>A (p.Arg1096His). Eculizumab was star ted, with an improvement being observed in a short time in the haemolysis, renal function, and clinical status, with some notable and unexpected beneficial effects on SSc.

Enfermedad invasiva asociada a neumococo y síndrome urémico hemolítico, nuevo serotipo / Invasive pneumococcal disease and hemolytic uremic syndrome: new serotype

El síndrome urémico hemolítico asociado a Streptococcus pneumoniae (SUH-Sp) se define como anemia hemolítica microangiopática, plaquetopenia y lesión renal aguda, en un paciente con infección invasiva por Streptococcus pneumoniae (Sp). Varón de 2 años, con neumonía con derrame pleural por Sp aislado en hemocultivos y líquido pleural. A las 72 h, presentó palidez, decaimiento, quejido respiratorio y oliguria. En el análisis de laboratorio se encontró anemia, plaquetopenia, aumento de la urea, la creatinina y la lactato deshidrogenasa en sangre; coombs directa +; esquistocitos en frotis; fibrinógeno; coagulograma normal; dímero D aumentado. Orina con proteinuria y hematuria. En Terapia Intensiva requirió asistencia respiratoria mecánica y transfusión con glóbulos rojos lavados; se recuperó progresivamente. El Instituto Malbrán informó serotipo 38 de Sp. Es el primer paciente comunicado con este serotipo

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury, in a patient with Streptococcus pneumoniae (Sp) invasive infection. A 2-year-old boy was admitted with pneumonia and empyema. Sp was isolated from blood and pleural fluid cultures. After 72 h, the patient showed paleness, asthenia, respiratory whining and oliguria. Laboratory showed anemia, low platelets, increased blood urea, creatirnina, lactate dehdrogenase, direct Coombs +, schistocytes, fibrinogen, normal coagulogram and increased D-dimer. Proteinuria and hematuria were detected in urine. Mechanical ventilatory assistance and transfusions of washed red blood cells were required. The patient recovered progressively. Sp serotype 38 was isolated in the National Reference Laboratory "Malbran". This is the first report associated to this serotype

An Stx-EAEC O59:NM[H19] strain isolated from a hemolytic uremic syndrome case in Argentina / Cepa EAEC-Stx O59:NM[H19] aislada de un caso de síndrome urémico hemolítico en Argentina

Abstract Shiga toxin-producing Escherichia coli (STEC) are a heterogeneous group of foodborne pathogens causing a broad spectrum of human disease, from uncomplicated diarrhea to hemolytic uremic syndrome (HUS). In this study, we report an HUS case associated with an O59:NM H19 mstrain, harboring stx2a, iha, lpfAO26, lpfAO113 genes associated with STEC, and aatA, aap, pic, sigA, agg4A genes associated with enteroaggregative E. coli (EAEC), named Stx-EAEC. The strain showed low toxicity on Vero cells, and was resistant to streptomycin and trimethoprim/sulfonamides. The child carried the bacteria for more than 100 days. Since the large outbreak associated with Stx-EAEC O104:H4, many strains with similar profiles have been described. In Germany, an O59:NM[H19] strain, with comparable characteristics to the Argentine strain, was isolated from a bloody diarrhea case. In Argentina, this is the first report of an HUS case associated with a Stx-EAEC infection, and represents a new challenge for the surveillance system. © 2019 Published by Elsevier Espana, S.L.U. on behalf of Asociacion Argentina de Microbiolog´a. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/ licenses/by-nc-nd/4.0/).

Resumen Escherichia coli productor de la toxina Shiga (STEC) es un grupo heterogéneo de patógenos transmitidos por alimentos que causan un amplio espectro de enfermedades humanas, desde diarrea no complicada hasta síndrome urémico hemolítico (SUH). Nosotros informamos de un caso de SUH por O59:NM[H19], que portaba los genes stx2a, iha, lpfAo26, lpfAoii3 asociados con STEC, y los genes aatA, aap, pic, sigA, agg4A de E. coli enteroagregativo (EAEC), llamado EAEC-Stx. La cepa mostró baja citotoxicidad en las células Vero, y fue resistente a estreptomicina y trimetoprima/sulfonamidas. El niño excretó la bacteria durante más de 100 días. Desde el brote asociado con EAEC-Stx O104:H4, se describieron muchas cepas con perfiles similares. En Alemania se aisló una cepa O59:NM[H19] de una diarrea sanguinolenta, con características comparables a la cepa argentina. Este es el primer informe de un caso de SUH asociado a una infección por EAEC-Stx, y representa un nuevo desafío para el sistema de vigilancia. © 2019 Publicado por Elsevier Espana, S.L.U. en nombre de Asociación Argentina de Microbiología. Este es un artículo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Síndrome urémico hemolítico y yogur: entre la creencia popular y la evidencia científica / Hemolytic uremic syndrome and yoghurt: popular belief and scientific evidence

Algunos profesionales de la salud desaconsejan el consumo del yogur por el riesgo de provocar Síndrome Urémico Hemolítico, una enfermedad grave causada por cepas de E. coli productor de toxina Shiga (STEC por sus siglas en inglés). Estas bacterias pueden pasar del intestino del ganado vacuno a la carne o a la leche en condiciones inadecuadas de trabajo en frigoríficos o establecimientos productores de leche, respectivamente, siendo las hamburguesas insuficientemente cocidas el principal vector de la enfermedad y la leche cruda sin pasteurizar o los productos lácteos elaborados con ésta, otro factor de riesgo. En la industria láctea, el yogur se elabora con leche que es sometida a un doble tratamiento térmico. En la bibliografía moderna reportes de la presencia de STEC en yogures industriales, y los trabajos de revisión y meta-análisis no incluyen al yogur, pero sí a la leche sin pasteurizar, como vectores de trasmisión de STEC. En este contexto, y dada la evidencia científica disponible actualmente en relación a E. coli productor de toxina Shiga, el SUH y el yogur, parecería que estamos ante la presencia de una correlación espuria, la asociación de dos hechos que no tienen relación causal entre sí, más que a un hecho científico del cual uno (el yogur) es el responsable del otro (SUH).

Some health professionals discourage yogurt because of the risk of Hemolytic Uremic Syndrome (HUS), a serious disease caused by strains of Shiga toxin-producing E. coli (STEC). These bacteria can pass from the intestine of cattle to meat or milk under inadequate working conditions in slaughterhouses or milking plants. Undercooked hamburgers the main is vector of disease and unpasteurized raw milk or dairy products made with it, are another risk factors. In the dairy industry, yoghurt is made from milk that undergoes a double heat treatment. There are no reports of the presence of STEC in industrial yogurts in the modern bibliography, and reviews and meta-analysis do not point to yogurt as a risk factor for STEC, but rather unpasteurized milk. In this context, and given the scientific evidence currently available regarding STEC, HUS and yogurt, it would seem that we are in the presence of a spurious correlation, the association between two facts that have no causal relationship between them, rather than a scientific fact for which one (yogurt) may be responsible for the other (HUS).

Hemolytic uremic syndrome associated with streptococcus pneumoniae in pediatrics: a case series / Síndrome hemolítico-urêmica associada com streptococcus pneumoniae em pediatria: série de casos

ABSTRACT Objective: To describe a case series of four (4) patients with hemolytic uremic syndrome due to Streptococcus pneumoniae in a level four complexity institution in the city of Bogotá, D.C., Colombia. Cases description: We describe cases of four patients who presented respiratory symptoms and fever. All four patients were in regular conditions on hospital admission, after which they required intensive care and ventilatory support. Upon admission, three cases showed evidence of pleuropulmonary complication. Penicillin-sensitive Streptococcus pneumoniae was isolated in all cases. All patients presented anemia, severe thrombocytopenia, schistocytes on peripheral blood smear, and hyperazotemia. They required blood transfusion and renal replacement therapy during their hospitalization. The patients were diagnosed with hemolytic uremic syndrome due to S. pneumoniae. Three of the four patients had a progressive recovery of the renal function and were discharged after an average of 36 days of hospital stay. The remaining patient had two amputations in the extremities due to thrombotic vascular complications and was discharged after 99 days of hospital stay, requiring hemodialysis every other day. Comments: Hemolytic uremic syndrome due to Streptococcus pneumoniae is a rare but severe complication of invasive pneumococcal disease. Complicated pneumonia is the main condition associated with this entity. It is noteworthy the short period in which these cases were presented, considering the low annual incidence of the disease.

RESUMO Objetivo: Descrever uma série de casos de quatro pacientes com síndrome hemolítico-urêmica por pneumococo em uma instituição de referência em Bogotá, Colômbia. Descrição dos casos: Descrevemos os casos de quatro pacientes que apresentaram sintomas respiratórios e febre. Todos estavam em estado geral regular à admissão hospitalar e necessitaram de cuidados intensivos e suporte ventilatório. Na admissão, em três dos casos foi evidenciada a complicação pleuropulmonar. Isolamento de Streptococcus pneumoniae sensível à penicilina foi realizado em todos os casos. Os quatro pacientes precisaram de transfusão sanguínea e terapia de reposição renal durante a hospitalização. Nos testes laboratoriais, observou-se anemia, trombocitopenia grave, presença de esquizócitos em esfregaço de sangue periférico e hiperazotemia. Com esse quadro, o diagnóstico foi de síndrome hemolítico-urêmica associada à infecção por S. pneumoniae. Houve recuperação progressiva da função renal em três dos quatro pacientes, que tiveram alta após 36 dias de internação hospitalar, em média. Um paciente teve complicações vasculares trombóticas, resultando em duas amputações nas extremidades, e teve alta após 99 dias de internação, com necessidade de hemodiálise em dias alternados. Comentários: A síndrome hemolítico-urêmica por Streptococcus pneumoniae é uma complicação rara, mas grave, da doença invasiva pneumocócica. A pneumonia complicada é a principal condição associada a essa entidade. Destaca-se o curto período em que esses casos foram apresentados, levando em conta a baixa incidência anual de síndrome hemolítico-urêmica.

Uso do eculizumab na síndrome hemolítico urêmica atípica associada a comprometimento da função renal: revisão integrativa / Use of eculizumab in atypical hemolytic uremic syndrome associated with impaired renal function: integrative review

Introdução: a Síndrome Hemolítico Urêmica é uma doença rara e grave que se define pela anemia hemolítica microangiopática não imune, trombocitopenia e insuficiência renal aguda. Objetivo: identificar informações disponíveis na literatura acerca do uso do eculizumab no tratamento da síndrome hemolítico urêmica atípica com comprometimento da função renal associado. Material e métodos: trata-se de uma revisão integrativa realizada nas seguintes bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde e Medical Literature Analysis and Retrieval System Online. O estudo foi norteado pela seguinte questão: O que há na literatura acerca do uso do eculizumab no tratamento da SHUa com comprometimento da função renal? Para busca de artigos foram utilizados três descritores em português, inglês e espanhol. O recorte temporal foi de 2007 à 2017. Resultados:Inicialmente foram localizados dez artigos e após a aplicação dos critérios de inclusão e exclusão foram selecionados sete deles. Todos os artigos relatam melhora da função renal logo no início da terapia e não há consenso quanto a indicação de descontinuação do uso do eculizumab nesses pacientes, mesmo nos casos onde houve completa remissão da patologia. Conclusão: Ainda são poucos os estudos sobre o uso do eculizumab. Estudos dessa natureza tem relevante contribuição para o avanço da terapia em casos raros como a SHUa, tendo em vista que o uso do anticorpo pode aumentar a sobrevida e melhorar a qualidade de vida de pessoas acometidas com a doença.

Introduction: Hemolytic Uremic Syndrome is a rare and serious disease that is defined by non-immune microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Objective: To identify information available in the literature about the use of eculizumab in the treatment of atypical hemolytic uremic syndrome with impaired renal function. Material and methods: This is an integrative review carried out in the following databases: Latin American and Caribbean Literature in Health Sciences and Medical Literature Analysis and Retrieval System Online. The study was guided by the following question: What is there in the literature about the use of eculizumab in the treatment of atypical HUS with impaired renal function? Three descriptors were used to search for articles in Portuguese, English and Spanish. The time frame was from 2007 to 2017. Results: Ten articles were initially located, and seven of them were selected after the inclusion and exclusion criteria were applied. Ten articles were initially located, and seven of them were selected after the inclusion and exclusion criteria were applied. All articles report an improvement in renal function early in therapy and there isn't consensus regarding the indication of discontinuation of eculizumab in these patients, even in cases where there was complete remission of the condition. Conclusion: There are still few studies on the use of eculizumab. Studies of this nature have a relevant contribution to the advancement of therapy in rare cases, such as SHUa, since the use of antibody may increase survival and improve the quality of life of people affected by the disease.

Infecciones por Escherichia coli productora de toxina Shiga O121: H19 en pacientes atendidos en Mar del Plata / Infections caused by Escherichia coli producing Shiga O121: H19 toxin in patients treated in Mar del Plata

Escherichia coli productora de toxina Shiga (STEC) O157:H7 es el serotipo más frecuentemente identificado como agente causal de colitis hemorrágica y síndrome urémico hemolítico (SUH), aunque se han descripto más de 100 serotipos con potencial patogénico similar. El objetivo del trabajo fue describir casos de enfermedad humana asociados a la infección por STEC O121:H19, atendidos en la ciudad de Mar del Plata y establecer la relación genética de los aislamientos mediante técnicas de epidemiología molecular. Se observó un amplio espectro en la severidad clínica de los ocho casos estudiados: dos fueron asintomáticos (contactos de SUH), un paciente tuvo diarrea sanguinolenta, y cinco presentaron SUH. Uno de los pacientes con SUH falleció. Las cepas O121:H19 portadoras del genotipo stx2a/eae/ehxA fueron sensibles a los antibióticos ensayados y presentaron por electroforesis en gel de campo pulsado (Xbal-PFGE) distintos patrones de macrorrestricción, con similitud del 84,25%. El patrón AREXKX01.0072, detectado en un SUH y en su contacto, es nuevo en la Base de Datos Nacional de STEC no-O157 de la Argentina. La utilización de métodos estandarizados de detección y tipificación de STEC permite a los laboratorios de referencia monitorear la frecuencia temporal y la distribución geográfica de las cepas circulantes para la prevención y control de estos patógenos asociados a enfermedad humana.

Shiga toxin-producing Escherichia coli (STEC) O157:H7 is the most frequent serotype identified as causative agent of sporadic cases and outbreaks of diarrhea with or without blood, hemorrhagic colitis and hemolytic uremic syndrome (HUS), although more than 100 serotypes have been described of similar pathogenic potential. The aim of the study was to describe cases of human disease associated with STEC O121:H19 infections, assisted in Mar del Plata City, and to establish the genetic relationship of the isolates by molecular epidemiology techniques. A wide spectrum was observed in the clinical severity of the eight cases studied: two were asymptomatic (contacts of HUS), one patient had bloody diarrhea, and five cases presented HUS. One HUS case died. All STEC O121:H19 strains carried the stx2a/eae/ehxA genotype, were sensitive to all antibiotics tested and showed different macrorestriction patterns by pulsed-field gel electrophoresis (Xbal-PFGE), with 84.25% similarity. The pattern AREXKX01.0072, detected in a HUS case and in his contact, is new in the Argentine National Database of non-O157 STEC. The use of standardized methods for detection and typing of STEC allows reference laboratories to monitor the temporal frequency and geographical distribution of circulating strains for the prevention and control of these pathogens associated with human diseases.

Escherichia coli produtora de toxina Shiga (STEC) O157:H7 é o sorotipo mais frequentemente identificado como o agente causador de colite hemorrágica e síndrome hemolítica urêmica (SHU), embora tenham sido descritas mais de 100 sorotipos com potencial patogênico semelhantes. O objectivo foi o de descrever os casos de doença humana associadas com a infecção por STEC O121:H19, assistido, na cidade de Mar del Plata e estabelecer relação genética de isolados utilizando epidemiologia molecular. Um amplo espectro foi observado na severidade clínica dos oito casos estudados, dois eram assintomáticos (contacto SHU), uma paciente teve diarreia com sangue, e cinco tiveram SHU. Um caso de SHU faleceu. As cepas O121:H19 portaram o genótipo stx2a/eae/ehxA, foram sensíveis aos antibióticos testados e apresentaram, por eletroforese em gel de campo pulsado (Xbal-PFGE), diferentes padrões de macrorestrição, com similaridade de 84,25%. O padrão AREXKX01.0072 detectado em SHU e em seu contato, é novo para a Base de Dados Nacional de STEC não-O157 na Argentina. O uso de métodos padrão de detecção e tipagem de STEC permite os laboratórios de referência monitorar frequência temporal e distribuição geográfica de estirpes circulantes para a prevenção e controlo destes agentes patogénicos associados com a doença humana.

Síndrome hemolítico urémico asociado a Shigatoxina: ¿Cómo prevenirlo? / Shiga-toxin associated hemolytic uremic syndrome: how to prevent it?

Resumen: El síndrome hemolítico urémico (SHU) asociado a infección intestinal por bacterias productoras de Shigatoxina, que afecta principalmente a población infantil, puede causar morbilidad aguda grave, secuelas crónicas en varios órganos, y la muerte prematura en algunos de ellos. Dado su carácter zoonótico, adecuadas medidas de manejo agropecuario y correcta higiene de lo que consumimos es indispensable a la hora de prevenir la infección. Actualmente, una vez gatillado el SHU el manejo es médico y, principalmente, de soporte. En los últimos años diversas estrategias terapéuticas se han ido desarrollando para evitar que esta enfermedad ocurra, o, al menos, que pueda ser atenuada en sus consecuencias de morbi-mortalidad. El presente artículo describe acciones específicas a diferentes niveles de prevención de esta patología.

Abstract Hemolytic uremic syndrome (HUS) associated with intestinal infection by Shiga toxin-producing bacteria, which mainly affects children, can cause severe acute morbidity, chronic sequelae in seve ral organs, and premature death in some of them. Given its zoonotic nature, adequate measures of agricultural management and proper hygiene of what we consume are essential to prevent infection. Once the HUS is triggered, medical management is currently mainly supportive. In recent years, va rious therapeutic strategies have been developed to prevent this disease from occurring or, at least, to mitigate its morbidity and mortality consequences. This article describes specific actions at different levels of prevention of this pathology.

Differential Diagnosis and Treatment of Thrombotic Microangiopathy Syndrome / 대한내과학회지

Diagnosis of thrombotic microangiopathy (TMA) is challenging due to its close association with other forms of microangiopathic hemolytic anemia, such as malignant hypertension and disseminated intravascular coagulation, and because other manifestations including cytopenia and acute kidney injury are manifestations of other medical comorbidities. Further challenges for accurate diagnosis include distinguishing between primary and secondary TMA, as well as between hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). TTP is typically differentiated from HUS by the presence of more severe thrombocytopenia, along with a higher frequency of altered mental status with relatively preserved renal function. However, the clinical course can vary among patients, requiring polymerase chain reaction testing of patient stools for enterohemorrhagic Escherichia coli and a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) assay. To reduce the mortality rate, prompt initiation of plasmapheresis is important in cases where TPP cannot be excluded. Future advances enabling more rapid testing for ADAMTS13 levels will reduce the need for unnecessary plasmapheresis, so that treatment strategy can be more optimized.