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

Síndrome Dress relacionada ao uso de Alopurinol: relato de caso / Dress Syndrome related to the use of allopurinol: case report

A síndrome DRESS é uma reação adversa a medicamentos pouco conhecida dentro da prática clínica, porém com grande potencial de letalidade devido a combinação de manifestações cutâneas e envolvimento de múltiplos órgãos. Objetivo: identificar possíveis reações adversas graves e incomuns secundárias ao uso de medicações usadas frequentemente na prática clínica. Métodos: Trata-se de um relato de caso construído com base em levantamento de dados do prontuário do paciente e análise a partir de um referencial teórico para comprovação de sua relevância na prática clínica. Resultado: Enfatizou-se a importância de um reconhecimento precoce dessa condição, a fim de evitar desfechos graves

The DRESS syndrome is an adverse drug reaction that is unsual in clinical practice, but with a high potential for lethality, due to the combination of cutaneous manifestations and involvement of multiple organs. Objective: identify possible serious and unusual adverse reactions secondary to the use of medications frequently used in clinical practice. Methods: This is a case report built on the basis of data collection from the patient's medical record and analysis from a theoretical framework to prove its source in clinical practice. Outcome: The importance of early recognition of this condition was emphasized, in order to avoid serious outcomes

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.

HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

Drug Eruptions Induced by Allopurinol Associated with HLA-B*5801.

Allopurinol, a drug commonly used for treating gout and hyperuricemia, is a frequent cause of drug eruptions. Recent investigations suggest that HLA‑B*5801 allele is a very strong marker for allopurinol‑induced cutaneous adverse drug reactions (cADRs). In this article we report two cases of allopurinol‑induced drug eruptions in patients carrying the HLA‑B*5801 allele and review the literature on the association between HLA‑B*5801 and allopurinol‑induced cADRs based on a MEDLINE and PubMed search.

Allopurinol hypersensitivity syndrome in patients with hematological malignancies: characteristics and clinical outcomes

BACKGROUND/AIMS: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. METHODS: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. RESULTS: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the HLA-B*5801 allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. CONCLUSIONS: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.

Allopurinol-induced DRESS syndrome mimicking biliary obstruction

An 84-year-old man was admitted to our hospital with fever, jaundice, and itching. He had been diagnosed previously with chronic renal failure and diabetes, and had been taking allopurinol medication for 2 months. A physical examination revealed that he had a fever (38.8degrees C), jaundice, and a generalized maculopapular rash. Azotemia, eosinophilia, atypical lymphocytosis, elevation of liver enzymes, and hyperbilirubinemia were detected by blood analysis. Magnetic resonance cholangiography revealed multiple cysts similar to choledochal cysts in the liver along the biliary tree. Obstructive jaundice was suspected clinically, and so an endoscopic ultrasound examination was performed, which ruled out a diagnosis of obstructive jaundice. The patient was diagnosed with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome due to allopurinol. Allopurinol treatment was stopped and steroid treatment was started. The patient died from cardiac arrest on day 15 following admission.

Necrólise epidérmica tóxica desencadeada por alopurinol: relatode caso / Toxic epidermal necrolysis initiated by allopurinol: case report

JUSTIFICATIVA E OBJETIVOS: A necrólise epidérmica tóxica (NET) é uma farmacodermia rara, com possibilidade de morte pelas suas complicações. O objetivo deste relato foi apresentar um caso desta farmacodermia devido ao uso de alopurinol, um medicamento de uso comum. RELATO DO CASO: Paciente do sexo masculino, 65 anos, apresentou o quadro após utilização de alopurinol concomitante a uso pregresso de grande quantidade de álcool diariamente,anti-hipertensivos e diclofenaco irregularmente. Admitido no serviço com lesões descamativas de aspecto de grande queimado em mais de 50% do corpo, dispneia, taquicardia, hematúria macroscópica e conjuntivite bolhosa. O paciente foi tratado na unidade de terapia intensiva, com suspensão da medicação e teve boa evolução, com resolução total do quadro após 32 dias do seu início. CONCLUSÃO: O tratamento para NET ainda não é consensual, assim como a suspensão do medicamento que a originou. Entretanto, cuidados preferencialmente em unidades de queimado e prevenção e profilaxia com antibióticos para infecções são essenciais para uma boa evolução. O conhecimento médico sobre esta rara síndrome e sobre o seu tratamento adequado pode fazer a diferença no diagnóstico diferencial e na sua conduta.

BACKGROUND AND OBJECTIVES: Epidermal toxic necrolysis (TEN) is a rare dermatological reaction to drugs, feasible to death due to medical complications. This article reports a caseof such reaction due to the use of allopurinol, a rather common drug.CASE REPORT: Male patient, 65 year old, presenting the reaction after the use of allopurinol along with previous daily ingestion of great amounts of alcohol, antihypertensive medications, and irregular diclofenac. He was admitted with desquamating lesions similar to skin burns in over 50% of body surface, dyspnea, tachycardia, macroscopic hematuria and bullosa conjunctivitis.The patient was taken care of in the Intensive Care Unit, his medication was suspended and he improved importantly, resolving the reaction after 32 days since its initial development. CONCLUSION: There is no consensus for the treatment of TEN, a neither as for the medication suspension. However, intensive care in burns unit and prevention and prophylaxis with antibiotics for infections are essential for good resolution. Knowing such rare syndrome and its adequate treatment might makethe difference during the differential diagnosis and conducts.

A case of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis / 대한간학회지

Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.

A Case of Vanishing Bile Duct Syndrome Associated with Hypersensitivity to Allopurinol / 대한간학회지

Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome.

Efeitos do alopurinol em rins isquêmicos de cäes anestesiados com pentobarbital sódico / Effects of allopurinol in ischemic kidneys of dogs anesthetized with sodium pentobarbital

Justificativa e objetivos: o alopurinol é droga que inibe a formaçäo de radicais livres lesivos ao rim. O objetivo deste estudo foi verificar o efeito protetor renal do alopurinol em rins isquêmicos de cäes. Método em 16 cäes, anestesiados com pentobarbital sódico (PS) e submetidos à expansäo do volume extracelular (1,4mlkg(elevado a menos 1).min(elevado a menos 1)), à respiraçäo mecânica com ar ambiente, à nefrectomia direita e ao pinçamento da artéria renal esquerda foram estudadas as alteraçöes que poderiam ocorrer na morfologia e funçäo renal após período de trinta minutos de total isquemia e posterior reperfusäo, no grupo 1(G1), bem como a açäo do alopurinol (50mg.kg(elevado a menos 1) sobre estes rins, administrado 24 horas antes do experimento e uma hora antes da realizaçäo de isquemia no grupo 2 (G2). Os atributos estudados, frequência cardíaca, pressäo da cava inferior, pressäo arterial média, depuraçäo de PAH, fluxo sanguíneo renal, resistência vascular renal, depuraçäo de creatina, fraçäo de filtraçäo, débito urinário, osmolalidade plasmática e urinária, depuraçäo esmolar, de água livre, de sódio e de potássio, excreçäo urinária e fracionária de sódio e de potássio, hematócrito, temperatura retal e exame histológico do rim esquerdo foram pesquisados em quatro momentos: M1, momento controle, M2, M3 e M4 obtidos respectivamente, imediatamente, 15 e 30 minutos após a liberaçäo da artéria renal esquerda. Em G2 a obtençäo de M1, M2, M3 e M4 ocorreu 45, 90, 105 e 120 minutos após a 2a. dose do alopurinol. Resultados: em M1 de ambos os grupos, ocorreram os maiores valores para o Cpah, FSR e Ccr e os menores valores para o RVR. Os animais mantiveram-se taquicárdicos desde o início do experimento, tanto em G1 quanto em G2. Os demais parâmetros näo se alteraram. O exame histológico do rim esquerdo mostrou-se alteraçöes compatíveis com necrose tubular aguda em ambos os grupos experimentais. Conclusöes: as alteraçöes encontradas na hemodinâmica renal säo compatíveis com a liberaçäo de substâncias vasoconstritoras pela isquemia renal. O alopurinol näo se mostrou eficaz em prevenir as alteraçöes renais decorrentes da isquemia e reperfusäo

Influencia do alopurinol na evolucao da nefropatia induzida por adriamicina / Alopurinol in evolution of nephropathy induced for adriamycin

A influencia do ion superoxido na evolution da nefropatia por adriamicina foi avaliada usando-se alopurinol para inibir sua sintese.Sessenta ratos Wistar machos foram divididos em 6 grupos.No primeiro dia do experimento 3 grupos receberam salina(GCS,GCSTA eGCSTC) e 3 receberam adriamicina(GNC,GNTA,GNTC)Dois grupos(GCSTA eGNTA)foram tratados com alopurinol 3 horas antes e 1 minuto depois da inoculacao com salina(GCTA) ou adriamicina(GNTA).em dois grupos adicionais o tratamento com alopurinol foi mantido ate o fim do experimento(4 semanas).Os grupos tratados com adriamicina apresentaram proteinuria macica da semana 2 ate a semana 4.Apenas na semana 2 observou-se diferenca estatistica entre a proteinuria dos tres grupos tratados com adriamicina.((GNC=129,2+ou -17,5mg/24h:GNTA=85,4+ ou -15,9mg/24h:GNTC=87,8+ ou -15,9mg/24h;p maior0,01)A microscopia optica os animais inoculados com adriamicina apresentaram somente lesoes tubulo-intersticiais tais como cilindros intratubulares,dilatacao e atrofia tubular e infiltrado inflamatorio intersticial.Nao houve diferenca significativa do indice de lesao tubulo-interstitical entre os tres grupos nefroticos(GNC=8;GNTA=6;GNTC=4;p menor0,05).Conclusao:Em ratos com nefropatia por adriamicina,o uso de alopurinol associou-se com diminuicao transitoria da proteinuria,mas nao alterou a lesao tubulo-intersticial

Síndrome de hipersensibilidad por alopurinol: un caso de necrosis hepática masiva / Allopurinol hypersernsitivity syndrome: a case with massive hepatic necrosis

Los efectos o reacciones adversas a medicamentos, dependiendo del órgano blanco, tienen diversas manifestaciones clínicas que varían de grado e intensidad. Debido a que la piel es un órgano visible y fácil de explorar, las dermatosis por medicamentos son una complicación frecuente y en ocasiones forman parte de un padecimiento sistémico. Se discute el caso de una mujer de 72 años con antecedente de automedicación con alopurinol a dosis no especificadas, dos semanas previas al inicio de los síntomas. El cuadro clínico se caracterizó por dermatosis generalizada con daño renal y hepático. Posteriormente la enfermedad desarrolló síndrome de Stevens-Johnson, insuficiencia renal, hepatitis tóxica con necrosis masiva corroborada por biopsia transyugular; además cursó con choque cardiogénico y hemorragia del tubo digestivo como eventos finales. La paciente falleció y no se realizó el estudio postmórtem. El curso clínico y las complicacione en nuestra paciente corresponden al síndrome de hipersensibilidad al alopurinol. La relevancia del caso se basa en la extensión del daño hepático, el cual es un efecto tóxico infrecuente por este medicamento. El síndrome de hipersensibilidad al alopurinol es una complicación impredecible y grave

Combination therapy in Kala-azar.

128 untreated cases of Kala-azar were divided in 4 equal groups of 32, Group A was treated with Sodium Stibogluconate (SSG) in the dose of 20 mg/kg/body wt. for 30 days. Group B was treated SSG plus allopurinol in the dose of 20 mg/kg/body wt. orally in divided dosage for 30 days. Group C received SSG plus Ketoconazole 600 mg orally in divided dosage for 30 days. Group D in addition to SSG also received levamisole in single oral daily dose of 13 mg/kg/body wt. for 30 days. Response of Group B, C and D was compared to Group A. Results from this study revealed combination of allopurinol with SSG to be statistically not superior to SSG alone.

Efectos del Allopurinol sobre el riñón: su relación con los radicales libres del oxígeno / Effect of allopurinol over the kidney: oxygen free radical relation

Para dilucidar los mecanismos tóxicos responsables de la nefrotoxicidad inducida por el Allopurinol y las respuestas protectoras endógenas, se investigaron las variaciones de la Creatinina plasmática, la peroxidación lipídica renal, los factores de producción de radicales libres del O2: xantina oxidasa y sus sustratos: xantina e hipoxantina y los factores de eliminación de tales radicales: superóxido dismutasa y catalasa. Las ratas recibieron subcutáneamente inyecciones de Allopurinol en dosis de 100 mg/kg de peso, por día y durante tres días. Comparando ratas normales, se observaron los siguientes cambios: a) un aumento en las proporciones de creatinina plasmática y en los niveles tisulares de la catalasa y de la supeóxido dismutasa; c) los valores máximos y mínimos se observaron al tercer día de administración de la droga y posteriormente todos los parámetros se normalizan a sus niveles originales; d) estos resultados sugieren que la nefrotoxicidad del Allopurinol se atribuiría al aumento de la peroxidación lipídica, que por un lado, aumenta la producción de radicales libres del O2, y por otro lado, estarían dismunuidos los mecanismos de su eliminación

Insuficiência renal aguda em leishmaniose tegumentar americana tratada com a associaçäo glucantime e alopurinol / Acute renal insufficiency in mucocutaneous leismaniasis reated with glucantime and allopurinol

Os autores apresentam um caso de leishmaniose tegumentar americana causada por Leishmânia viannia brasiliensis que de um grupo de seis pacientes tratados com a associaçäo glucantime e alopurinol desenvolveu quadro de nefrite intersticial aguda acompanhado de exantema cutâneo. Questionam se näo houve potencializaçäo na interaçäo das drogas com relaçäo ao efeito desejável