Síndrome DRESS inducido por ácido valproico en una niña que respondió a la ciclosporina con análisis de HLA / Valproic acid-induced DRESS in a child responding to cyclosporine with HLA analysis

El síndrome de erupción medicamentosa con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms, DRESS), también conocido como síndrome de hipersensibilidad inducida por medicamentos, es una reacción rara potencialmente mortal que causa una erupción grave y que puede provocar insuficiencia multiorgánica. Como con otras erupciones medicamentosas graves, los linfocitos T específicos para un medicamento tienen una función crucial en el síndrome DRESS. El modelo de hapteno/pro-hapteno, el modelo de interacción farmacológica y el modelo alterado de repertorio de péptidos son tres modelos diferentes desarrollados para describir la relación/interacción entre un medicamento o sus metabolitos y el sistema inmunitario. Analizamos nuestra experiencia con el tratamiento con ciclosporina en un caso de síndrome DRESS resistente a esteroides causado por ácido valproico en una niña y sus resultados clínicos, de laboratorio y de antígeno leucocitario humano (HLA).

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is a potentially life-threatening rare reaction that causes a severe rash and can lead to multiorgan failure. As in other severe drug eruptions, drug-specific T lymphocytes play a crucial role in DRESS. The hapten/pro-hapten model, pharmacological interaction model, and altered peptide repertoire model are three different models developed to describe the relationship/interaction between a medication or its metabolites and the immune system. We discuss our experience with cyclosporine treatment in a steroid-resistant DRESS syndrome caused by valproic acid in a girl, as well as her clinical, laboratory, and human leukocyte antigens (HLA) study results

Síndrome de DRESS inducido por sulfasalazina. ¿Consideramos esta reacción adversa grave al indicar el fármaco? Caso clínico

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe, rare and potentially lethal idiosyncratic condition associated with the use of some drugs. Given its broad spectrum of presentation, clinical suspicion is essential for management, since it requires the immediate withdrawal of the culprit drug, support measures and the use of corticosteroids as the first line of treatment. We report a 24-year-old woman with a diagnosis of ulcerative colitis with joint involvement despite the use of infliximab, who presented symptoms, signs and laboratory compatible with DRESS syndrome on the third week after indicating sulfasalazine for her baseline disease.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina: Caso pediátrico / Drug reaction with eosinophilia and systemic symptoms due to carbamazepine: Pediatric case

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000-10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000-10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

Drug reaction with eosinophilia and systemic symptoms (DRESS) and its relation with autoimmunity in a reference center in Mexico

Abstract: BACKGROUND: Drug reaction with eosinophilia and systemic symptoms is a severe adverse drug reaction, with a reported mortality of 10%. Long-term outcomes involve organic failure and autoimmune diseases in some populations. OBJECTIVE: To evaluate the clinical prognosis of patients with drug reaction with eosinophilia and systemic symptoms. METHODS: We conducted a retrospective review at a referral hospital in Mexico City in a period of 22 years (1992-2013), looking up for records with diagnosis of DRESS according to RegiSCAR criteria. Clinical characteristics, organ failures, culprit drugs, treatment, and short and long-term sequelae were analyzed. RESULTS: We found 11 patients with diagnosis of drug reaction with eosinophilia and systemic symptoms syndrome, 7 female and 4 male, with a median age of 22 years-old; 9 had maculopapular rash and 2 were erythrodermic. Affected organs were liver (8/11), kidney (6/11) and hematologic disorders (8/11). The most common culprit drugs were antiepileptic (63%). Systemic corticosteroids were given to 8 patients, being pyelonephritis (1/8) and pneumonia (2/8) the adverse events of this therapy. Long-term sequelae were 1 patient with renal failure, 1 patient with chronic anemia; and 2 patients developed autoimmune diseases (one autoimmune thyroid disease and another one with autoimmune thyroid disease and autoimmune hemolytic anemia). Study limitations: The retrospective nature of the study and the limited number of patients with drug reaction with eosinophilia and systemic symptoms. CONCLUSIONS: Drug reaction with eosinophilia and systemic symptoms syndrome has been linked to the development of chronic organ failure. We found two young patients who developed autoimmune diseases in the short term. Patients with drug reaction with eosinophilia and systemic symptoms should have a long-term monitoring for signs or symptoms suggestive of an autoimmune disease.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos en pediatría: Caso clínico / DRESS syndrome in paediatrics: Clinical case

El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos es una enfermedad potencialmente mortal, caracterizada por exantema, fiebre, adenopatías, alteraciones hematológicas y compromiso de órganos internos. Objetivo: Presentar una afección poco frecuente en pediatría para facilitar la sospecha diagnóstica y el rápido reconocimiento por parte de los médicos. Caso clínico: Lactante de 9 meses hospitalizada por un cuadro de neumonía viral grave con ventilación mecánica no invasiva, tratada con ceftriaxona entre otros medicamentos. Al quinto día de suspendido el antibiótico presentó un exantema maculopapular violáceo, confluente de predominio en el tronco, la cara y las extremidades superiores, asociado a fiebre, eosinofilia y elevación de transaminasas. Se manejó con prednisona oral más corticoides tópicos por 6 semanas, con buena evolución a los 3 meses de seguimiento. Conclusiones: El diagnóstico de síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos se realiza por clínica y exámenes de laboratorio, además de biopsia cutánea en caso de duda diagnóstica. Si bien su causa más frecuente son los anticonvulsivantes se han descrito casos con un sinnúmero de fármacos. El manejo consiste en la suspensión del fármaco sospechoso asociado a medidas de soporte y tratamiento corticosteroide por tiempos prolongados.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, haematological abnormalities, lymphadenopathy, and internal organ involvement. Objective: Presenting a rare condition in children, to facilitate a rapid diagnostic suspicion and recognition by doctors. Case report: An 9 months old infant admitted due to a severe viral pneumonia, managed with non-invasive ventilation and ceftriaxone. Five days after stopping antibiotics, a confluent maculopapular rash appeared, which was predominantly in the trunk, face and upper extremities, combined with a fever, eosinophilia, and elevated serum levels of transaminase. She received treatment with oral prednisone and topical corticosteroids for 6 weeks, with a good outcome after 3 months. Conclusions: The diagnosis of DRESS syndrome is made using clinical criteria, laboratory values, and histopathology, if there is any query. Although it is classically caused by anticonvulsants and sulphonamides, many other drugs have been implicated. The offending drug should be immediately discontinued and the patient given supportive treatment, and systemic corticosteroids for long periods of treatment.

Infección por virus herpes humano 6 en un paciente inmunocompetente con síndrome DRESS secundario a carbamazepina / Human herpes virus 6 infection in an inmunocompetent patient with carbamazepine-induced DRESS syndrome

El síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) constituye una reacción adversa a fármacos, potencialmente mortal, caracterizada por una erupción cutánea polimorfa asociada a fiebre, linfadeno-patías y compromiso multiorgánico con eosinofilia. Presentamos el caso clínico de un hombre inmunocompetente con un síndrome DRESS secundario a carbamazepina que cursó concomitantemente con una meningoencefalitis por virus herpes humano 6 (VHH-6). El rol patogénico del VHH-6 en el síndrome DRESS sigue siendo controversial; sin embargo, dada la importancia diagnóstica y eventualmente pronóstica de la infección por VHH-6, su tamizaje sería recomendable dentro del estudio de estos pacientes.

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is an adverse life-threatening drug reaction characterized by a polymorphous rash associated with fever, lymphadenopathy and multiorgan involvement with eosinophilia. We present the case of an immunocompetent man with DRESS syndrome secondary to carbamazepine, that developed concomitantly meningoencephalitis caused by human herpes virus 6 (HHV-6), and a review of literature. The pathogenic role of HHV-6 in DRESS syndrome remains controversial. Given the diagnostic and possibly prognostic significance of HHV-6, the screening seems to be a good measure to use in the clinical management of these patients.

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) / Reação a drogas com eosinofilia e sintomas sistêmicos (síndrome DRESS)

SUMMARY Objective: To review the hypersensitivity reaction to drugs known as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), based on a case report. We also intend to discuss the difficulty and importance of disease recognition, since none of the changes is pathognomonic of this disease and failure to identify it may have disastrous consequences for the patient. Method: To describe this case report, in addition to the information collected for clinical assessment, a literature review was performed in the PubMed and Bireme databases in order to retrieve the latest information published in literature on DRESS syndrome. Results: The case of a 20-year old patient is reported. After anamnesis, physical examination and laboratory tests a diagnosis of DRESS syndrome was performed, characterized by rash, hematologic alterations, lymphadenopathy and lesions in target organ. This is a rare syndrome, whose frequency varies according to the drug used and the immune status of the patient, being more often associated with the use of anticonvulsants. Conclusion: The approach and discussion of the topic are of paramount importance, in view of the potential lethality of this treatable syndrome. Recognizing the occurrence of DRESS syndrome and starting treatment as soon as possible is crucial to reduce the risk of mortality and improve prognosis.

RESUMO Objetivo: fazer uma revisão da reação de hipersensibilidade a drogas denominada reação a drogas com eosinofilia e sintomas sistêmicos (síndrome DRESS), com base em um relato de caso clínico. Pretende-se ainda discutir a dificuldade e importância de seu reconhecimento, uma vez que nenhuma alteração dessa doença é patognomônica e sua não identificação pode trazer consequências desastrosas para o paciente. Método: para descrever este relato, além das informações coletadas no caso clínico, uma revisão da literatura nas bases de dados PubMed e Bireme foi realizada com o intuito de rever as informações mais recentes publicadas na literatura acerca da síndrome DRESS. Resultados: relatou-se o caso de uma paciente de 20 anos de idade que, após anamnese, exame físico e exames laboratoriais, foi diagnosticada com síndrome DRESS, caracterizada por erupção cutânea, alterações hematológicas, linfonodomegalia e lesões em órgão-alvo. É uma síndrome rara, cuja frequência varia conforme a droga utilizada e o estado imunológico do indivíduo, sendo mais associada ao uso de anticonvulsivantes. Conclusão: a abordagem e discussão do tema são de extrema importância, tendo em vista o potencial de letalidade dessa síndrome, que possui tratamento. Reconhecer precocemente a DRESS e instituir terapêutica é fundamental para reduzir o risco de mortalidade e melhorar o prognóstico.

DRESS syndrome in ophthalmic patients / Síndrome DRESS em pacientes oftalmológicos

ABSTRACT Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal adverse drug reaction associated with skin rash, fever, eosinophilia, and multiple organ injury. A number of pharmacological agents are known to cause DRESS syndrome such as allopurinol, anticonvulsants, vancomycin, trimethoprime-sulfamethoxazole, and pyrimethamine-sulfadiazine. Here, we describe two patients who developed DRESS syndrome during ocular treatment. The first case was being treated for late postoperative endophthalmitis with topical antibiotics, intravenous cephalothin, meropenem, and intravitreal injection of vancomycin and ceftazidime before symptoms developed. We were unable to identify the causal drug owing to the large number of medications concurrently administered. The second case presented with DRESS syndrome symptoms during ocular toxoplasmosis treatment. In this case, a clearer association with pyrimethamine-sulfadiazine was observed. As a result of the regular prescription of pharmacological agents associated with DRESS syndrome, ophthalmologists should be aware of the potentially serious complications of DRESS syndrome.

RESUMO Síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) é uma reação adversa a medicamentos rara e potencialmente fatal, associada à rash cutâneo, febre, eosinofilia e lesão de múltiplos órgãos. Algumas drogas podem desencadeá-la, como: alopurinol, anticonvulsivantes, vancomicina, sulfametoxazol-trimetoprim, sulfadiazina-pirimetamina, entre outras. Descrevemos dois casos que desenvolverem DRESS síndrome durante tratamento ocular. O primeiro caso apresentou os sintomas durante tratamento para endoftalmite pós-operatória tardia com antibióticos tópicos, cefalotina e meropenem intravenosos e injeção intravítrea de vancomicina e ceftazidima; não podemos identificar a droga causadora, pois múltiplas medicações foram utilizadas. O segundo caso desenvolveu os sintomas durante tratamento clássico para toxoplasmose ocular, então a associação com sulfadiazina-pirimetamina foi mais clara. Como muitos oftalmologistas prescrevem regularmente drogas que podem desencadear a síndrome DRESS, esse diagnóstico deve ser lembrado já que pode levar a sérias complicações.

Reacción por drogas con eosinofilia y síntomas sistémicos (síndrome de DRESS): Estudio retrospectivo de nueve casos / Dress syndrome: Report of nine cases

Background: DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is an uncommon disease caused by drugs. It is characterized by a polymorphic disseminated eruption with fever and multiple organ dysfunction. Aim: To report the etiology, characteristics, treatment, prognosis, and follow up of patients with DRESS Syndrome admitted to a clinical hospital. Material and Methods: Review of medical records of patients admitted for drug reactions, selecting those patients complying with clinical criteria for DRESS Syndrome. Drugs used during three months prior to the onset of symptoms were evaluated as possible causes of the disease. Results: Nine patients aged 16 to 68 years (six males) complied with the clinical criteria for the disease. The causative medications were carbamazepine in three patients, phenytoin in three, antituberculous drugs in two and amoxicillin in one. All were treated with systemic steroids with a complete clinical resolution. Conclusions: DRESS syndrome is usually underdiagnosed and has a good response to systemic steroids.

Reacciones cutáneas adversas a antimicrobianos sistémicos en pacientes hospitalizados: estudio transversal analítico retrospectivo / Inpatient cutaneous adverse reactions to systemic antibiotics: an analytical cross-sectional retrospective study

Introduction: The reported literature about the types of cutaneous adverse antibiotic reactions (ATB-CAR) and the responsible antimicrobial class is scarce. Aim: to describe the clinical and histopathological profile of these reactions, and potential associations between different types of ATB-CAR and causal antibiotic class in a tertiary hospital in Chile. Material and Methods: Cross-sectional retrospective study performed at the Hospital of the Pontificia Universidad Católica de Chile. Results: A total of 58 patients were included. The most common type of ATB-CAR was morbilliform (n: 37, 63.8%). The antibiotics most frequently involved were the penicillins and cephalosporins (n: 34, 69.3%). The most common histological pattern in all types of ATB-CAR was superficial perivascular dermatitis with or without spongiosis. There was significant association between urticarial, morbilliform, DRESS and PEGA types, with the use of penicillins, cephalosporins, cotrimoxazole, and lincomycin, respectively (n: 4,100%, n: 15, 40.5%, n: 2; 50%, n: 1, 50%, p < 0.05, respectively). Discussion: This is the first description of the ATB-CAR patterns in South American hospitalized patients. Both clinical and histopathological patterns of ATB-CAR are similar to other published series, however the types of causal antibiotics are different.

Introducción: La literatura médica reportada acerca de los tipos de reacciones cutáneas adversas a antimicrobianos (ATM-cRAM) y la clase de antimicrobiano responsable es escasa. Objetivo: Describir el perfil clínico e histopatológico de estas reacciones, y establecer posibles asociaciones entre los distintos tipos de ATM-cRAM y la clase de antimicrobiano causal, en un hospital terciario en Chile. Material y Método: Estudio transversal analítico retrospectivo realizado en el Hospital de la Pontificia Universidad Católica de Chile. Resultados: Fue incluido un total de 58 pacientes. El tipo más frecuente de ATM-cRAM fue el morbiliforme (n: 37; 63,8%). Los antimicrobianos más frecuentemente implicados fueron penicilinas y cefalosporinas (n: 34; 69,3%). El patrón histopatológico más frecuente en todos los tipos de ATM-cRAM fue el de dermatitis perivascular superficial, con o sin espongiosis. Hubo asociación significativa entre las ATM-cRAM tipo urticaria, morbiliforme, DRESS y PEGA, con el uso de penicilinas, cefalosporinas, cotrimoxazol y lincomicina, respectivamente (n: 4,100%; n: 15, 40,5%; n: 2; 50%; n: 1; 50%, p < 0,05, respectivamente). Discusión: Este estudio corresponde a la primera descripción de los patrones de ATM-cRAM en pacientes hospitalizados sudamericanos. Tanto los patrones clínicos como histopatológicos de ATM-cRAM son similares a otras series publicadas; sin embargo, los tipos de antimicrobianos causales no coinciden con lo previamente descrito.