Síndrome de DRESS asociado al consumo de alopurinol: reporte de caso

El síndrome de DRESS (por sus siglas en inglés Drug Reaction with Eosinophilia and Systemic Symptoms) representa una farmacodermia grave con diferentes manifestaciones clínicas y paraclínicas secundarias a una reacción de hipersensibilidad farmacológica. Su incidencia exacta es desconocida pero se estima entre 1 a 1000 y 1 a 10000 casos de exposición a fármacos asociados. Se caracteriza por dermatosis generalizada extensa en conjunto con afección orgánica, linfadenopatia, eosinofilia y linfocitosis atípica. Entre los fármacos comúnmente asociados se encuentran anticomiciales aromáticos, carbamazepina, sulfonamidas y el alopurinol. Mediante el uso de la puntuación RegiSCAR es posible confirmar o descartar una sospecha de diagnóstico. El tratamiento depende de la severidad de presentación incluyendo esteroides tópicos hasta esteroide sistémico de duración variable dependiendo respuesta clínica y bioquímica. Se reporta tasas de mortalidad del 10 al 20% siendo la insuficiencia hepática la principal causa de muerte en estos pacientes. Se presenta el caso de un paciente femenino de 71 años de edad que, posterior a tratamiento con alopurinol, debuta con eritrodermia secundaria a Síndrome de DRESS.

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) represents severe pharmacodermia with different clinical and paraclinical manifestations secondary to a drug hypersensitivity reaction. The exact incidence is unknown, but it is estimated to be between 1 in 1,000 and 1 in 10,000 cases of exposure to associated drugs. It is characterized by extensive generalized dermatosis, in conjunction with organic involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. Commonly associated drugs include aromatic anticonvulsants, carbamazepine, sulfonamides, and allopurinol. By using the RegiSCAR score, it is possible to confirm or rule out a suspected diagnosis. Treatment depends on the severity of presentation, including topical steroids to systemic steroids of variable duration, depending on clinical and biochemical responses. Mortality rates of 10 - 20% have been reported, with liver failure being the main cause of death in these patients. We present the case of a 71-year-old female patient who, after treatment with allopurinol, developed erythroderma secondary to DRESS Syndrome.

¿Debemos manejar la hiperuricemia asintomática para proteger al riñón?

Contexto: el ácido úrico es el producto final de la degradación de las purinas en los primates, en condiciones normales es un agente antioxidante endógeno y participa en varias vías fisiológicas, sin embargo, cuando los niveles séricos de urato se incrementan, estos participan en el desarrollo de diversas enfermedades. Desde el siglo XIX se conoce de la asociación entre hiperuricemia y daño renal, aunque ninguna guía de manejo recomienda el uso de fármacos hipouricemiantes en pacientes asintomáticos, en algunos casos especiales, el manejo farmacológico beneficiará a pacientes con hiperuricemia, brindando protección al riñón y disminuyendo el riesgo de desarrollar enfermedad renal terminal. Objetivo: describir la relación entre hiperuricemia y daño renal, y analizar los casos en los que el manejo de esta condición con medicamentos resultará en un beneficio para el riñón de los pacientes. Metodología: revisión de la literatura sobre la participación de la hiperuricemia en el daño renal y análisis de los artículos revisados. Resultados: el manejo de la hiperuricemia asintomática puede proteger el riñón en algunas situaciones específicas. Conclusiones: hay situaciones específicas para la disminución de los niveles séricos de ácido úrico.

Background: Uric acid is the end product of purine degradation in primates, under normal conditions it is an endogenous antioxidant agent and participates in several physiological pathways. However, when serum urate levels are increased, they participate in the development of various diseases. Since the nineteenth century, the association between hyperuricemia and kidney damage has been known. Although no management guideline recommends the use of hypouricemic drugs in asymptomatic patients, in some special cases pharmacological management will benefit patients with hyperuricemia, providing protection to the kidney and decreasing the risk of developing end-stage renal disease. Purpose: To describe the relationship between hyperuricemia and kidney damage, and to analyze the cases in which the management of this condition with medications will result in a benefit for the kidney of patients. Methodology: Review of the literature on the involvement of hyperuricemia in kidney damage, analysis of the reviewed articles. Results: Management of asymptomatic hyperuricemia may protect the kidney in some specific situations. Conclusions: There are specific situations for the decrease of serum uric acid levels.

Research advances in the therapeutic potential of xanthine oxidoreductase inhibitors for periodontitis / 口腔疾病防治

@#Periodontitis is associated with abnormal purine metabolism, which is manifested by increased uric acid in host blood and increased expression of the purine-degrading enzyme, xanthine oxidoreductase (XOR), in periodontal tissues. Both XOR and uric acid are pro-oxidative and pro-inflammatory mediators under pathological conditions. Animal studies have found that injection of uric acid promotes the progression of periodontitis and that febuxostat (an XOR inhibitor) improves tissue destruction in periodontitis. Therefore, blocking the source of uric acid may be a therapeutic strategy to control the progression of periodontitis. In this article, the rationality of XOR inhibitors as potential therapeutic drugs for periodontitis is reviewed. The literature review results suggest that XOR inhibitors show antioxidative, anti-inflammatory, and anti-osteoclastic effects, and XOR inhibitors show clinical efficacy in the treatment of infectious, inflammatory and osteolytic diseases. Although there is no direct evidence to support the finding that XOR inhibitors can ameliorate periodontal microecological dysbiosis, these drugs can modulate intestinal microflora dysbiosis, and there is indirect evidence to support a beneficial effect of XOR inhibitors on periodontal microecological dysbiosis. In conclusion, XOR inhibitors may be used as immunomodulators for the adjuvant treatment of periodontitis by inhibiting inflammation, oxidative stress and anti-osteoclast effects.

Características del síndrome de lisis tumoral en pacientes pediátricos oncológicos. Un estudio observacional de centro único / Characteristics of tumor lysis syndrome in pediatric oncology patients. A single-center observational study

Introducción:El síndrome de lisis tumoral (SLT) es una emergencia oncológica, que produce alteraciones en el metabolismo, causando manifestaciones clínicas y trastornos bioquímicos que ponen en peligro la vida del paciente.El objetivo del presente estudio fue identificar las características clínicas, de laboratorio y tratamiento del SLT, en pacientes pediátricos onco-lógicos, del Instituto del Cáncer SOLCA-Cuenca, en el periodo 2010 ­2020.Materiales y métodos:En este estudio se identificó las características del SLT, en pacientes pediátricos oncológicos, del Instituto del Cáncer SOLCA-Cuenca, en el periodo 2010 ­2020, a través de un estudio de tipo descriptivo-observacional.Resultados:Seincluyó 463 historias clínicas, en el cual se obtuvo que el SLT tuvo una frecuen-cia del 5.61 %, con predominio del sexo masculino (57.7%) y con una edad media de 7 ± 1.29 años. La presentación clínica más observada fue la deshidratación con náusea, vómito y dia-rrea (57.7%). Las alteraciones de laboratorio más frecuentes fueron la hiperuricemia y la hi-pocalcemia, con un 76.9 %y un 73.1 %respectivamente. La Leucemia linfoblástica aguda (LLA) fue el diagnósticooncológico con más casos (61.5 %). Los pilares del tratamiento fue-ron la hiperhidratación y el uso de alopurinol, utilizados en el 100% y un 80.8 %respectiva-mente.Conclusión:El SLT afectó más frecuentemente a varones, con diagnóstico de leucemia, ma-nifestaciones clínicas digestivas y alteraciones de laboratorio (hiperuricemia e hipocalcemia). El tratamiento empleado resultó eficaz y se basó en lo recomendado por la literatura médica

Introduction:Tumor lysis syndrome (TLS) is an oncological emergency that results in meta-bolic alterations, causing clinical manifestations and biochemical disorders that endanger pa-tients' lives. The objective of the present study was to identify the clinical, laboratory, and treat-ment characteristics of TLSsin pediatric oncology patients at the SOLCA-Cuenca Cancer Ins-titute from 2010­2020.Materials and methods: In this study, the characteristics of TLS were identified in pediatric oncology patients at the SOLCA-Cuenca Cancer Institute from 2010 to 2020 through a des-criptive observational study.Results: A total of463 medical records were included. TLSs were associated witha frequency of 5.61%, with a predominance of males(57.7%) and a mean age of 7 ± 1.29 years. The most commonclinical presentation was dehydration with nausea, vomiting, and diarrhea (57.7%). The most frequent laboratory alterations were hyperuricemia and hypocalcemia, with 76.9% and 73.1%,respectively. The oncological diagnosis was acutelymphoblastic leukemia (ALL) in most patients(61.5%). The pillars of treatment were hyperhydration and allopurinol, used in 100% and 80.8%, respectively.Conclusion: TLSsmore frequently affectmen with a diagnosis of leukemia, digestive clinical manifestations, orlaboratory alterations (hyperuricemia and hypocalcemia). The treatment used was effective and based on what the medical literature recommended

Treatment of acquired perforant dermatoses with allopurinol / Tratamento de dermatose perfurante adquirida com alopurinol

Perforating dermatoses are papulonodular cutaneous pathologies characterized by transepithelial extrusion of components of the extracellular matrix of the dermis, by inflammation or degeneration. When secondary, the systemic diseases are called Acquired Perforating Diseases. Our letter aims to report a case of acquired perforating dermatoses secondary to chronic renal dialysis. The treatment with Allopurinol proved to be effective in this case. Allopurinol would act as an antioxidant, reducing the inflammatory reaction in tissues and consequent damage to the collagen fibers (AU)

Dermatoses perfurantes são patologias cutâneas papulonodulares que se caracterizam pela extrusão transepitelial de componentes da matriz extracelular da derme, por inflamação ou degeneração. Quando são secundárias as doenças sistêmicas são chamadas Doenças Perfurantes Adquiridas. Nossa carta tem como objetivo relatar caso de dermatose perfurante adquirida secundária a insuficiência renal crônica dialítica. O tratamento com Alopurinol se mostrou eficaz neste caso. O Alopurinol atuaria como antioxidante, reduzindo a reação inflamatória nos tecidos e consequentes danos nas fibras colágenas (AU)

Síndrome DRESS secundária ao uso de alopurinol: um relato de caso / DRESS syndrome secondary to the use of allopurinol: a case report

A Síndrome de DRESS (do inglês, Drug Rash with Eosinophilia and Systemic Symptoms) é uma patologia rara que consiste em uma severa reação medicamentosa mediada por células T. O presente relato de caso retrata uma paciente do sexo feminino, 59 anos, que apresentou icterícia, febre não termometrada, acolia, colúria, mialgia, placas hipercrômicas e lesões pruriginosas. Referiu uso recente de alopurinol, paracetamol e nimesulida, apresentando melhora importante e espontânea após a suspensão das medicações. A extensão do tempo de exposição ao medicamento agressor ocasiona um maior período de internação e risco de mortalidade. Além disso, os dados restritos sobre a Síndrome de DRESS impõe desafios ao seu diagnóstico. Sendo assim, este estudo busca destacar a importância do diagnóstico clínico precoce, a suspensão do medicamento agressor e a instituição da terapêutica adequada para um prognóstico favorável

The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a rare pathology that consists of a severe drug reaction mediated by T cells. The present case report depicts a female patient, 59 years old, who presented jaundice, non thermometered fever, acholia, choluria, myalgia, hyperchromic plaques and pruritic lesions. She mentioned recent use of allopurinol, paracetamol and nimesulide, showing significant and spontaneous improvement after discontinuation of medications. The extension of time of exposure to the offending drug causes a longer period of hospitalization and risk of mortality. In addition, the restricted data on DRESS Syndrome poses challenges to its diagnosis. Therefore, this study seeks to highlight the importance of early clinical diagnosis, suspension of the offending drug and the institution of appropriate therapy for a favorable prognosis

Efficacy and safety of allopurinol in the treatment of chronic kidney disease: a meta-analysis / 中国医师杂志

Objective:To evaluate the efficacy and safety of allopurinol in the treatment of chronic kidney disease.Methods:The databases of Embase, PubMed and the Cochrane library were searched for randomized controlled trials of allopurinol in patients with chronic kidney disease. According to the Cochrane system evaluation method, two evaluators independently screened the literature and extracted the data, and analyzed the results with Revman 5.3 software.Results:Finally, 10 articles were included, including 940 patients (472 in the experimental group and 468 in the control group). Meta analysis showed that allopurinol treatment could reduce blood uric acid ( MD=-2.40, 95% CI: -2.74--2.05, P<0.01), 24-hour urinary protein ( MD=-0.61, 95% CI: -1.17--0.06, P=0.03) and increase estimation of glomerular filtration rate(eGFR) ( MD=2.51, 95% CI: 1.86-3.17, P<0.01). There was no significant difference in adverse events between the experimental group and the control group ( OR=1.40, 95% CI: 0.61-3.19, P=0.42), but allopurinol treatment could reduce the risk of cardiovascular events ( OR=0.58, 95% CI: 0.38-0.89, P=0.01). Conclusions:Allopurinol treatment of chronic kidney disease can reduce urinary protein, improve eGFR, and reduce the risk of cardiovascular events.

Hyperuricemia and chronic kidney disease: to treat or not to treat / Hiperuricemia e doença renal crônica: tratar ou não tratar

Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.

Resumo A hiperuricemia é comum na doença renal crônica (DRC) e pode estar presente em até 50% dos pacientes que se apresentam para diálise. A hiperuricemia pode ser secundária ao comprometimento da taxa de filtração glomerular (TFG) que ocorre na DRC. No entanto, ela também pode preceder o desenvolvimento da doença renal e mesmo prever uma DRC incidente. Estudos experimentais de modelos hiperuricêmicos descobriram que tanto o ácido úrico solúvel quanto o cristalino podem causar danos renais significativos, caracterizados por isquemia, fibrose tubulointersticial e inflamação. Entretanto, a maioria dos estudos de randomização Mendeliana falhou em demonstrar uma relação causal entre o ácido úrico e a DRC, e os ensaios clínicos têm apresentado resultados variáveis. Aqui sugerimos explicações potenciais para os achados clínicos e genéticos negativos, incluindo o papel do ácido úrico cristalino, do ácido úrico intracelular e da atividade da xantina oxidase na lesão renal mediada por ácido úrico. Propomos ensaios clínicos futuros, bem como um algoritmo para o tratamento de hiperuricemia em pacientes com DRC.

Successful treatment of diffuse cutaneous leishmaniasis caused by Leishmania amazonensis

Abstract Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.

Estudio de utilización de fármacos antigotosos en población colombiana, 2016 / Patterns of anti-gout drug use in a Colombian population: 2016

RESUMEN Objetivo: Identificar las características clínicas de los pacientes con gota y la forma de utilización de los medicamentos antigotosos en Colombia. Métodos: Estudio de corte transversal en el que se analizaron 310 historias clínicas de pacientes atendidos en el último trimestre del 2016 y que recibieron un medicamento antigotoso. Se identificaron variables sociodemográficas, clínicas, farmacológicas, comorbilidades y paraclínicas. Para cada medicamento antigotoso se determinó si el uso fue según las recomendaciones aprobadas por la Federal Drug Administration (FDA). Se realizaron análisis descriptivos, bivariados y multivariados. Resultados: Se evaluaron pacientes de 14 diferentes ciudades de Colombia, con un predominio masculino del 70,3% (n = 218) y una mediana de edad de 64 arios (RIC: 26-94 arios). El antigotoso más frecuentemente utilizado fue alopurinol (n = 255; 82,3%), seguido de colchicina (n = 54; 17,4%). Los diagnósticos hallados como indicación fueron: hiperuricemia (n = 181; 58,4%), gota (n = 34; 11%), artritis gotosa (n = 28; 9%). El 74,5% (n = 231) de las prescripciones tenía un uso aprobado según la FDA, especialmente alopurinol en el manejo de gota e hiperuricemias, mientras que colchicina se encontró siendo utilizada en indicaciones no aprobadas (n = 44; 81,4%). Las comorbilidades más frecuentes fueron hipertensión (68,4%) y dislipidemia (55,8%). Conclusiones: Los pacientes con gota en tratamiento farmacológico tienen una elevada frecuencia de comorbilidades cardiovasculares, y están siendo tratados con alopurinol para la prevención a largo plazo, mientras que una menor proporción recibe colchicina que comúnmente es utilizada para indicaciones no aprobadas por las agencias reguladoras.

ABSTRACT Objective: To identify the clinical characteristics of patients with gout, and the prescription patterns of anti-gout medications in Colombia. Methods: Cross-sectional study, that analysed the data from 310 medical records of patients treated in the last quarter of 2016, and who received an anti-gout medication. Sociodemographic, clinical, pharmacological, comorbidities, and paraclinical variables were identified. For each anti-gout drug used, it was determined whether the use was in accordance with Federal Drug Administration (FDA) approved recommendations. Descriptive, bivariate and multivariate analyses were performed. Results: Patients from 14 different cities in Colombia were evaluated, with a male predominance of 70.3% (n = 218) and a median age of 64 years (RIC: 26-94 years). The most frequently used anti-gout medication was allopurinol (n = 255; 82.3%), followed by colchicine (n = 54; 17.4%). The main diagnoses found as an indication were: hyperuricaemia (n=181, 58.4%), gout (n = 34; 11.0%), and gouty arthritis (n = 28; 9.0%). Almost three-quarters (74.5%; n = 231) of the prescriptions had an approved use according to the FDA, especially allopurinol in the management of gout and hyperuricaemia, while colchicine was found to be used in unapproved indications (n = 44, 81.4%). The most frequent comorbidities were hypertension (68.4%) and dyslipidaemia (55.8%). Conclusions: Patients with gout who are under pharmacological treatment have a high frequency of cardiovascular comorbidities. They were being treated with allopurinol for long-term prevention, while a smaller proportion received colchicine, which is often used for indications not approved by regulatory agencies.

Effect of hyperuricemia treatment on vascular endothelial function in patients with cerebral infarction / 中华急诊医学杂志

Objective:To investigate the effect of hyperuricemia treatment on vascular endothelial function and blood pressure in patients with acute cerebral infarction.Methods:A total of 138 cases from the same center were enrolled in the study. 92 cases of acute cerebral infarction patients combined with hyperuricemia were selected. They were randomly divided into the experimental group (46 cases) and control group (46 cases). 46 cases of acute cerebral infarction patients with normal uric acid were selected in the same period. Patients in the experimental group received oral allopurinol for 3 months to treat hyperuricemia. Serum uric acid, blood lipid, and hs-CRP were tested before and after treatment in these populations. Blood pressure and body mass index (BMI) were also detected, and vascular endothelial function was evaluated using ultrasound non-invasive blood flow mediated vasodilation function (FMD). Comparison and statistical analysis were carried out in groups.Results:Uric acid [(479.7±49.0) μmol/L vs. (381.2±76.7) μmol/L]、hs-CRP[(8.1±6.7) mg/L vs. (5.1±4.6) mg/L]、systolic blood pressure [(124.7±26.3) mmHg vs. (97.4±13.5) mmHg] decreased significantly in the experimental group after 3 months of treatment with allopurinol ( P<0.05), and blood flow mediated vasodilation function [(7.6±3.5) vs. (11.2±3.9)]significantly increased ( P<0.05). The decrease of serum uric acid was positively correlated with the increase of FMD in the experimental group ( r=0.463, P<0.01). Multiple Regression analysis showed that serum uric acid was an independent predictor of FMD( β=-0.229, P=0.035). Conclusions:The treatment of hyperuricemia in patients with acute cerebral infarction can significantly improve the vascular endothelial function of patients, improve inflammation state and lower blood pressure. It is further confirmed that a higher uric acid level is related to worse endothelial function which may contribute to atherosclerosis.

Síndrome de DRESS secundario a alopurinol / DRESS syndrome secondary to allopurinol

RESUMEN El síndrome de hipersensibilidad por fármacos, también conocido como síndrome de DRESS, es una farmacodermia grave que se caracteriza por una erupción polimorfa diseminada, fiebre y compromiso multiorgánico. Este padecimiento tiene una incidencia que oscila entre el 0,1 % y el 0,01 % de las exposiciones farmacológicas, con una probabilidad de fallecimiento de un 20 % al 30 %. Fue descrito por primera vez en el año 1936, como una reacción adversa a la fenitoína. En la actualidad se reconoce que puede estar asociado a otros fármacos como: abacavir, metronidazol, doxiciclina, isoniazida, carbamacepina, fenobarbital, beta-bloqueadores, dapsona, ranitidina, antiinflamatorios no esteroideos y el alopurinol. Se presenta un paciente de 69 años de edad que desarrolló un síndrome de DRESS secundario a alopurinol. El paciente mostró signos poco frecuentes de esta rara enfermedad: linfocitos atípicos, hepatomegalia y afección renal; falleció poco después debido a un choque séptico por estafilococo áureo.

ABSTRACT Drug hypersensitivity syndrome, also known as DRESS syndrome, is a severe pharmacodermia characterized by a polymorphous disseminated rash, fever, and multi-organ involvement. Its incidence ranges between 0.1 to 0.01% from the pharmacological exposures, with a probability of death ranging from 20 to 30%. It was first described in 1936 as an adverse reaction to phenytoin. Nowadays, it is known that it can also be associated with other drugs such as abacavir, metronidazole, doxycycline, isoniazid, carbamazepine, phenobarbital, beta-blockers, dapsone, ranitidine, nonsteroidal anti-inflammatory drugs and allopurinol. We present a 69-year-old male patient who developed a DRESS syndrome secondary to alupurinol. The patient showed unusual signs of this rare disease such as atypical lymphocytes, hepatomegaly and kidney disease; he dies shortly after from a septic shock due to Staphylococcus aureus.

What is the Best Choice for Urate-lowering Therapy for Korean?

Gout is one of the most common forms of acute inflammatory arthritis caused by long-standing hyperuricemia. Various clinical and epidemiological studies have demonstrated that uric acid, which is strongly associated with the pathogenesis of gout, is closely related with increased cardiovascular (CV) risk. Thus, properly controlling uric acid levels within its physiological level using urate-lowering therapy has been hypothesized to improve CV outcomes. Recently, however, on the basis of the results of the largest prospective, the double-blind, randomized controlled trial, entitled “the Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES),” has aroused the possibility of increased CV-related and all-cause mortality in patients receiving febuxostat. Largely on the basis of this unpredicted result, the US and Korea Food and Drug Administration issued a public safety alert concerning the high risk of CV death with the use of febuxostat in February 2019. This unexpected announcement left many rheumatologists confused when they decide the first-line urate-lowering drug in Korea. In this review, we searched for previous studies on uric acid and increased risk of CV disease. In addition, we will introduce various interpretations of the results of the CARES trial and discuss the best choice of urate-lowering therapy for Korean.

Altered T cell and monocyte subsets in prolonged immune reconstitution inflammatory syndrome related with DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

Síndrome DRESS / DRESS syndrome

Resumen: El síndrome DRESS es un reacción de hipersensibilidad a fármacos severa e idiosincrásica, caracterizada por exantema, fiebre, adenopatías, alteraciones hematológicas y afectación de varios órganos. La heterogeneidad de la manifestación clínica representa un desafío diagnóstico para el médico clínico, se requiere alto índice de sospecha y descartar un amplio espectro de diagnósticos diferenciales. Las reacciones cutáneas asociadas con fármacos pueden ser cuadros potencialmente mortales, el diagnóstico oportuno puede modificar el pronóstico del paciente. Describimos el cuadro clínico y tratamiento de un paciente de 15 años con insuficiencia renal crónica que fue hospitalizado por lesiones morbiliformes generalizadas concomitantes con fiebre, linfadenopatías, esplenomegalia y eosinofilia. Descartar procesos infecciosos, autoinmunitarios y neoplásicos fue posible con estudios complementarios; el antecedente de ingestión reciente de alopurinol y los datos clínicos y de laboratorio permitieron establecer el diagnóstico definitivo de síndrome DRESS. El paciente recibió corticoesteroides tópicos y sistémicos, las manifestaciones clínicas revirtieron a partir de la segunda semana de hospitalización. Se insiste en la importancia de la identificación de factores de riesgo asociados con la aparición de este síndrome.

Abstract: Dress syndrome is a severe and idiosyncratic reaction of hypersensitivity to drugs, characterized by rash, fever, lymphadenopathy, hematological alterations and systemic compromise, the heterogeneity of the clinical presentation represents a diagnostic challenge for the clinician, a high clinical suspicion is required and the need to rule out a wide spectrum of differential diagnoses. Cutaneous reactions associated with drugs can be potentially fatal, early diagnosis can modify the patient's prognosis. We describe the clinical case and treatment of a 15-year-old male patient with chronic renal failure who was hospitalized for generalized morbilliform lesions associated with fever, lymphadenopathy, splenomegaly and eosinophilia. Complementary studies ruled out infectious, autoimmune and neoplastic processes; the antecedent of recent intake of allopurinol together with clinical and laboratory data allowed to establish a definitive diagnosis of DRESS syndrome. Patient received topical and systemic corticosteroids, clinical manifestations reverted from the second week of hospitalization. We emphasize the importance of identifying risk factors associated with the development of this syndrome.

The effect of graft application and allopurinol treatment on calvarial bone defect in rats

Abstract Purpose: To investigate the effects of allopurinol administration on osteoinductive reaction and bone development with graft material. Methods: Thirty-six Wistar albino rats were divided into 3 groups. In the control group, calvarial bone defect was only created without any treatment. In the Defect + Graft group, allograft treatment was performed by forming 8 mm calvarial bone defect. In the Defect + Graft + Allopurinol group, alloplastic bone graft was placed in the calvarial bone defect and then, allopurinol (50 mg/kg/day) treatment was intraperitoneally applied for 28 days. Results: Histopathological examination revealed inflammation, congestion in the vessels, and an increase in osteoclast cells in the defect area. We also observed that new osteocyte cells, increase in connective tissue fibers, and new bone trabeculae. Osteopontin expression was positive in osteoblast cells and lacunated osteocyte cells were located in the periphery of the new bone trabeculae. Osteopontin expression was also positive in osteoblasts and osteocytes cells of new bone trabeculae in the graft site. Conclusion: It has been shown that allopurinol treatment in rat calvaria defects may induce osteoblastic activity, matrix development, mature bone cell formation and new bone formation when used with autogenous grafts.

Systematic Evaluation and Meta-analysis of Efficacy and Safety of Different Doses of Febustrinol and Allopurinol in the Treatment of Gout / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of febustrin （80 mg/d and 40 mg/d） and allopurinol （300 mg/d） in the treatment of gout， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Embase， Cochrane library， CJFD， Wanfang database and CBM during from database establishment to Mar. 2019， randomized controlled trial （RCT） about efficacy and safety of febustrin 80 mg/d （trial group）， 40 mg/d （observation group） and allopurinol 300 mg/d （control group） in the treatment of gout were collected. After extracting data of clinical studies met inclusion criteria and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was conducted for blood uric acid decrease level， the compliance rate of serum uric acid concentration， incidence of liver dysfunction， incidence of renal dysfunction， incidence of digestive tract reaction and frequency of acute gout attack with Rev Man 5.1 software and Stata 13.0 software. RESULTS： A total of 17 RCTs were included， involving 1 816 patients. Meta-analysis results showed that， the serum uric acid decrease level of patients in trial group [MD＝－70.17， 95％CI （－97.41， －42.93）， P＜0.001] and the compliance rate of serum uric acid concentration [RR＝1.58， 95％CI （1.20， 2.08）， P＝0.001] were higher than observation group； the decrease of serum uric acid level [MD＝－34.68，95％（－61.35， －8.00）， P＝0.01] and the compliance rate of serum uric acid concentration [RR＝1.39，95％CI（1.04，1.85）， P＝0.03] in trial group were significantly higher than control group； the frequency of acute gout attack [RR＝1.54（1.02，2.31）， P＝0.04] in trial group was significantly higher than observation group. The incidence of liver dysfunction in observation group [RR＝0.71，95％CI（0.52，0.99），P＝0.04] was significantly lower than control group， with statistical significance. There was no statistical significance in other indexes among other indexes （P＞0.05）. CONCLUSIONS： Compared with febulostat 40 mg/d and allopurinol 300 mg/d， the efficacy of febulostat 80 mg/d is superior in reducing uric acid levels of gout patients.

Therapeutic potential of ethyl acetate fraction of Tephrosia purpurea Linn. leaves in a rat model of gout / 中西医结合学报

OBJECTIVE@#The present study is to determine the potential treatment effects of ethyl acetate fraction of Tephrosia purpurea Linn. leaves (EATP) against gout.@*METHODS@#Gout in experimental rats was induced with potassium oxonate at the dose of 250 mg/kg (intraperitoneal injection) for 7 consecutive days; EATP was administered 1 h after administration of the potassium oxonate on each day of experiment. Potassium oxonate was discontinued on the 8th day; thereafter allopurinol (10 mg/kg, p.o.) and EATP (200 and 400 mg/kg, p.o.) were continued until day 14. The uric acid level was measured from serum and urine during the experiment. Other biochemical parameters were assessed, including blood and urine creatinine, erythrocyte sedimentation rate, and total protein. Blood urea nitrogen, serum aspartate aminotransferase serum alanine aminotransferase and alkaline phosphatase were also measured. The blood was analyzed for levels of malondialdehyde and the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Histopathological and radiological changes in the ankle of rats were observed after completion of the experiment.@*RESULTS@#EATP was able to decrease serum uric acid and creatinine level; it also reduced inflammation, oxidative stress and lysosomal enzyme level, which has a role in acute inflammation. EATP increased uric acid excretion through urine due to its uricosuric effect.@*CONCLUSION@#EATP lowered the serum uric acid level and increased the urine uric acid level through excretion, which is useful in the treatment of gout. Hence the EATP was found to be helpful in the treatment of gout.

Hiperuricemia e hipertensión arterial sistémica: ¿cuál es la relación? / Hyperuricemia and systemic arterial hypertension: what is the relationship?

Resumen El ácido úrico es producto final del metabolismo de las purinas, transformadas finalmente a ácido úrico. No existe definición universal de hiperuricemia, en la práctica, el punto de corte es a partir de 6.8 mg/dL en plasma. Estudios experimentales han demostrado una correlación positiva lineal entre la presión arterial y las concentraciones de ácido úrico, así como disminución de las cifras tensionales al administrar tratamiento hipouricemiante con alopurinol. Se han identificado numerosos mecanismos a través de los cuales la hiperuricemia puede causar hipertensión: reducción de las concentraciones de óxido nítrico endotelial, estimulación de estrés oxidativo, expresión en las células de músculo liso del endotelio vascular de receptor URAT-1, activación del eje renina angiotensina, estimulación de la proliferación de músculo liso vascular, además, favorece la enfermedad microvascular renal. La evidencia reciente ha aportado nuevo conocimiento acerca de los múltiples mecanismos a través de los cuales el ácido úrico tendría un papel preponderante en la hipertensión arterial sistémica y en múltiples alteraciones metabólicas; sin embargo, hace falta desarrollar estudios clínicos a gran escala, bien diseñados, que comprueben de manera más contundente estas teorías, antes de considerar tratamientos enfocados en el manejo de la hiperuricemia asintomática en la práctica clínica diaria.

Abstract Uric acid is the end product of purine metabolism, ultimately converted to uric acid. There is no universal definition of hyperuricemia, in practice, the cutoff point is from 6.8mg/dL in plasma. The relationship between hyperuricemia and hypertension has been demonstrated in many experimental studies. Experimental studies have shown a linear positive correlation between blood pressure and uric acid levels, as well as a decrease in blood pressure figures with therapy with allopurinol. Numerous mechanisms have been identified through which hyperuricemia can cause hypertension: reduction of endothelial nitric oxide levels, stimulation of oxidative stress, expression in smooth muscle cells of the vascular endothelium of URAT-1 receptor, activation of the renin-angiotensin axis, stimulation of vascular smooth muscle proliferation also favors the development of renal microvascular disease. Recent evidence has provided new insight into the multiple mechanisms through which UA would play a major role both in systemic arterial hypertension and in multiple metabolic alterations; however, large-scale, well-designed clinical studies are needed, which prove more conclusively these theories, before considering therapies focused on the management of asymptomatic hyperuricemia in daily clinical practice

Comparison of influence of allopurinol and febuxostat on IL-1β and NALP3 levels and liver and kidney function in gout patients with hyperuricemia / 中国基层医药

Objective@#To study the influence of allopurinol and febuxostat on IL-1β and NALP3 levels and liver and kidney function in gout patients with hyperuricemia.@*Methods@#A total of 108 patients with stable gout accompanied by hyperuricemia were selected and randomly divided into control group and observation group according to the digital table, with 54 cases in each group.The control group was given allopurinol 100mg/time, orally, 3 times/d.The observation group was given febuxostat 40mg/time, orally, 1 time/d.The two groups were treated 4 weeks for 1 course, continuous treatment for 6 courses.The contents of serum IL-1β and NALP3, and renal function[creatinine(Scr), urea nitrogen(BUN), glomerular filtration rate(GFR) and uric acid(UA)], liver function[alanine aminotransferase(ALT) and aspartate aminotransferase(AST)]of the two groups were detected, and the adverse reaction of the two groups were observed.@*Results@#After treatment, the contents of serum IL-1β and NALP3 of the observation group decreased gradually, which were lower than those of the control group(t=1.910, 2.196, 4.954, 1.732, 5.944, 7.935, all P<0.05). After treatment, the blood UA of the two groups decreased significantly, the blood UA of the observation group was lower than the control group(t=9.772, P<0.05). The other kidney function indicators had no statistically significant differences between the two groups (t=0.082, 0.923, 1.395, all P>0.05). The liver function indicators of the two groups had no statistically significant differences(t=0.860, 0.563, all P>0.05). The incidence rate of adverse reactions in the observation group was 5.77%, which was lower than 20.75% in the control group(χ2=5.101, P=0.024).@*Conclusion@#Febuxostat in the treatment of gout with hyperuricemia can effectively reduce the level of serum UA, and inhibit the expression of inflammatory factors such as IL-1β and NALP3, with high safety, which is worthy of clinical promotion.