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

Reacción a fármacos con eosinofilia y síntomas sistémicos (DRESS) / Drug reaction with eosinophilia and systemic symptoms (DRESS)

La reacción a fármacos con eosinofilia y síntomas sistémicos (del acrónimo en inglés DRESS: drug reaction with eosinophilia and systemic symptoms) o síndrome de hipersensibilidad inducida por fármacos (del acrónimo en inglés DIHS: drug induced hypersensitivity syndrome), es una reacción adversa a fármacos (RAF) grave e infrecuente. Los mecanismos involucrados en su fisiopatogenia incluyen diversas alteraciones de las enzimas metabolizadoras de fármacos, con la consecuente acumulación de metabolitos reactivos, la reactivación secuencial de virus de la familia del herpes, la predisposición genética asociada a ciertos alelos de antígenos leucocitarios humanos (HLA) y una respuesta de hipersensibilidad retardada de tipo IV. En la actualidad, se han ido incorporando nuevos fármacos responsables de este cuadro como medicamentos biológicos, inmunosupresores y quimioterápicos. La presentación clínica del DRESS es variable. Tiene una morbimortalidad alta y supone costos elevados en la atención médica. Su tratamiento consiste, en primer lugar, en la suspensión de los fármacos causales o sospechosos de desencadenar el síndrome. Luego, según la gravedad del cuadro, se pueden indicar corticosteroides sistémicos o inmunoglobulina (IGIV) combinada con corticosteroides, plasmaféresis, ciclosporina, micofenolato de mofetilo y rituximab. El objetivo de este trabajo fue realizar una revisión sobre el DRESS y destacar los aspectos nuevos y relevantes de los últimos 5 años.

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), is a serious and rare adverse drug reaction. Among the mechanisms involved in its pathophysiology, there are various alterations in drugmetabolizing enzymes with the consequent accumulation of reactive metabolites, sequential reactivation of viruses of the herpes family, genetic predis-position associated with certain HLA, and a type IV hypersensitivity response. Currently, new drugs responsible for this pathology have been incorporated, such as biologicals, immunosuppressants and chemotherapy. The clinical presentation of DRESS is variable. It has a high morbidity and mortality and involves high costs in medical care. Its treatment consists, in the first place, in the suspension of the causal or suspected drugs. Then, depending on severity, systemic corticosteroids or IVIG combined with corticosteroids, plasmapheresis, cyclosporine, mycophenolate mofetil, and rituximab may be indicated.The objective of this work was review DRESS and highlight the new and relevant aspects of the last 5 years.

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 de intolerancia a múltiples medicamentos / Syndrome of intolerance to multiple medicines

El síndrome de intolerancia a múltiples medicamentos (MDIS, por sus siglas en inglés) se caracteriza por la intolerancia a dos o más medicamentos no relacionados. Tiene una prevalencia baja y es común en pacientes con polifarmacia. A pesar de que las reacciones adversas a los medicamentos son muy frecuentes, es raro que los pacientes debuten con este síndrome, el cual tiene implicaciones clínicas de leves a graves que afectan su vida; de acuerdo con esto varían el abordaje y su manejo. La sintomatología presentada varía desde síntomas gastrointestinales como reflujo gastroesofágico, dolores musculares y cefalea, hasta síntomas cutáneos; estos son los más frecuentes, tales como urticaria y erupciones maculopapulares o presentaciones menos comunes como el síndrome de Stevens-Johnson. El MDIS es causado por una amplia variedad de fármacos; por ello el conocimiento del síndrome, así como un adecuado interrogatorio de los antecedentes del paciente, es necesario para realizar un diagnóstico oportuno e instaurar un manejo adecuado y preventivo, evitando reacciones adversas que pongan en riesgo su vida. Con los hallazgos del cuadro clínico en la paciente, y basados en los antecedentes alérgicos presentados anteriormente a diferentes medicamentos no relacionados entre ellos, más la presentación de un rash maculopapular generalizado posterior a la administración de trimetoprim/sulfametoxazol se realiza el diagnóstico de MDIS. Se decide cambiar de medicamento por fosfomicina, con una consecuente evolución favorable. (AU)

Drug Reaction with eosinophilia and systemic symptoms with alopecia universalis and vitiligo / Reação a drogas com eosinofilia e sintomas sistêmicos associada a alopecia universal e vitiligo

ABSTRACT: Drug reactions with eosinophilia and systemic symptoms (DRESS) are rare and potentially fatal adverse hypersen-sitivity reaction to some drugs, especially anticonvulsants.The syndrome affects not only the skin but also other organs, especially the liver. The incidence can vary from 1 to 5 cases per 10.000 patients exposed to anticonvul-sants. The recognition of the syndrome is of fundamental importance since the mortality rate is between 10 and 40%. Once the diagnosis is established, the triggering drug must be identified and discontinued. Corticosteroids are usually associated with therapy. Autoimmune sequelae have been reported, including vitiligo and rarely alopecia. Alopecia universalis is a variant of alopecia areata, characterized by hair loss throughout the body. We report a case of DRESS, associated with two autoimmune dermatological diseases: alopecia universalis and vitiligo. (AU)

RESUMO: A reação a drogas com eosinofilia e sintomas sistêmicos (DRESS) é uma rara e potencialmente fatal reação adversa de hipersensibilidade, decorrente de alguns medicamentos, principalmente os anticonvulsivantes. A síndrome não afeta apenas a pele, mas também outros órgãos, principalmente o fígado. A incidência pode variar de 1 a 5 casos por 10.000 pacientes expostos aos anticonvulsivantes. O reconhecimento da síndrome é de fundamental importân-cia devido a taxa de mortalidade entre 10-40%. Uma vez estabelecido o diagnóstico, deve-se identificar o medica-mento desencadeante e suspendê-lo. O corticosteróide geralmente é associado na terapia. Sequelas autoimunes foram relatadas, incluindo vitiligo e raramente alopecia. A alopecia universal é uma variante da alopecia areata, caracterizada pela perda de pelos em todo o corpo. Relatamos um caso de DRESS, associado a duas doenças au-toimunes dermatológicas: alopecia universal e vitiligo. (AU)

Síndrome de Reacción a drogas con Eosinofilia y Síntomas Sistémicos (DRESS) asociados a Nefritis Túbulo Intersticial Aguda en un adolescente / DRESS síndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) associated with Tubulo Interstitial Nephritis in a adolescent

Resumen El síndrome de DRESS (Reacción a drogas con eosinofilia y síntomas sistémicos) es una patología poco frecuente en Pediatría, descrita por primera vez en 1996, por Bocquet. Puede presentarse en un tiempo variable luego de exposición a algunos medicamentos, se caracteriza por fiebre, compromiso cutáneo y de órganos internos. En este caso, se presenta a un paciente de 13 años, con antecedente de uso de Trimetroprim sulfa desde hace 2 meses, con cuadro de 3 días consistente en fiebre y rash cutáneo, sin compromiso de mucosas, con respuesta no favorable al manejo con esteroide, requiriendo Inmunoglobulina IV. Semanas después del inicio de los síntomas y evolución estable presenta insuficiencia renal aguda que requirió terapia de reemplazo renal. Se descartaron otras patologías subyacentes de índole autoinmune. Hubo recuperación de azoados y normalización de los demás paraclínicos el día 40 de la enfermedad. El paciente continúa asintomático, 4 meses después, con tratamiento con esteroide oral, en descenso lento y gradual. Se debe considerar la evaluación permanente de las pruebas de función renal en los pacientes que presenten Síndrome de DRESS, por su asociación con Nefritis intersticial aguda y complicaciones relacionadas.

Abstract DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a rare pathology in Pediatrics, first described in 1996 by Bocquet. It can appear in a variable period of time after exposure to some medications, it is characterized by fever, skin involvement and internal organs. A 13-year-old patient is presented, with a history of use of Trimethoprim sulfa for two months, with a disease of three days of evolution, consisting of fever and skin rash, without mucosal involvement, with an unfavorable response to steroid management, requiring Intravenous inmunoglobulin. Weeks after the onset of symptoms and stable evolution, he presented acute renal failure that required renal replacement therapy. Other underlying autoimmune pathologies were ruled out. There was recovery of renal function test and normalization of the other paraclinical on day 40 of the disease. Patient remains asymptomatic four months later, with oral steroid treatment, in slow and gradual decline. Permanent evaluation of renal function tests should be considered in patients with DRESS syndrome, due to its association with acute tubulointerstitial nephritis and related complications.

Síndrome DRESS por paracetamol / DRESS syndrome due to acetaminophen

A síndrome DRESS é uma entidade rara e distinta, caracterizada por acometimento cutâneo e envolvimento de órgãos internos, com risco potencial de morte. O diagnóstico e o tratamento pre- coces são de vital importância. Relatos de DRESS por paraceta- mol são raros na literatura, razão pela qual apresentamos este caso. Paciente do sexo masculino, 56 anos, com surgimento de rash maculopapular, febre, linfadenopatia e hipereosinofilia 3 semanas após suspensão de paracetamol, associados ao ante- cedente familiar de reação a fármaco. Evoluiu bem após pulso- terapia com metilprednisolona.

DRESS syndrome is a rare and distinct entity characterized by cutaneous manifestations and internal organs involvement with a potential risk of death. Early diagnosis and treatment are vi- tally important. Reported cases of DRESS syndrome due to ace- taminophen are rare in the literature, and that is the reason for this case report. A 56-year-old male patient with maculopapular rash, fever, lymphadenopathy, and hypereosinophilia three we- eks after suspension of acetaminophen, associated with a family history of drug reaction. It progressed well after pulse therapy with methylprednisolone.

Síndrome de DRESS en una paciente con fibrosis quística: reporte de un caso pediátrico / DRESS syndrome in a patient with cystic fibrosis: a pediatric case report

El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos o síndrome de DRESS según sus siglas en inglés (drug reaction with eosinophilia and systemic symptoms) se encuentra entre las reacciones medicamentosas cutáneas graves. Este consiste en una tríada clínica que incluye fiebre, exantema y compromiso sistémico, acompañado de eosinofilia y/o linfocitos atípicos.Se presenta el caso de una paciente de sexo femenino con fibrosis quística, de 18 meses de edad, quien desarrolló esta patología durante un tratamiento con trimetoprima-sulfametoxazol para erradicar Staphylococcus aureus meticilino resistente en esputo. Los pacientes con fibrosis quística reciben múltiples esquemas antibióticos según bacteriología en secreciones respiratorias para evitar el deterioro de la función pulmonar y colonización por gérmenes resistentes. Es menester conocer y sospechar este síndrome, debido al riesgo incrementado de hipersensibilidad a drogas en fibrosis quística, pronóstico ominoso y su elevada morbimortalidad

Drug reaction with eosinophilia and systemic symptoms or DRESS syndrome is among severe cutaneous drug reactions. This constitutes a clinical triad that includes fever, skin rash and systemic compromise, accompanied by eosinophilia and/or atypical lymphocytes.We present the case of an 18-month-old female patient with cystic fibrosis, who develops this pathology during a trimethoprim-sulfamethoxazole cycle as an eradicating treatment of methicillin-resistant Staphylococcus aureus in bronchial secretions. Cystic fibrosis patients receive multiple antibiotic regimens according to bacteriology in sputum, to avoid impairment in their lung function and colonization by resistant germs. Due to the increased risk of drug hypersensitivity in cystic fibrosis, an ominous prognosis and high morbidity and mortality, knowledge and a high index of suspicion of this syndrome are necessary

Síndrome de reacción a drogas con eosinofilia y síntomas sistémicos asociado a herpesvirus humano 6. Caso pediátrico tratado con ciclosporina y corticoides / Drug reaction with eosinophilia and systemic symptoms syndrome associated with human herpesvirus 6. A pediatric case treated with cyclosporine and corticosteroids

La reacción a drogas con eosinofilia y síntomas sistémicos es una reacción adversa cutánea rara, potencialmente grave. Puede presentar fiebre, erupción cutánea polimorfa, edema facial y/o linfoadenopatías. La reactivación del virus herpes humano tipo 6 se asocia a un curso más grave y/o prolongado.Un lactante de 22 meses en tratamiento con fenobarbital presentó lesiones eritematopapulares, fiebre, leucocitosis, proteína C reactiva elevada y alteración de pruebas hepáticas. Se realizó biopsia de piel compatible con reacción adversa a drogas. Se trató con corticoides sistémicos e inmunoglobulina intravenosa sin respuesta. La reacción en cadena de la polimerasa para virus herpes humano tipo 6 resultó positiva. Se inició ciclosporina más prednisona, con buena respuesta. Existe poca evidencia del uso de ciclosporina en adultos, cuando los corticoides sistémicos son inefectivos. Este es el primer reporte pediátrico Podría ser una alternativa efectiva o un complemento de los corticosteroides sistémicos cuando no responde a tratamientos convencionales.

Drug reaction with eosinophilia and systemic symptoms is a rare and potentially serious skin adverse reaction, with fever, polymorphous skin rash, facial edema, and/or lymphadenopathy. Reactivation of human herpes virus type 6 has been associated with a more severe and/or prolonged course. A 22-month-old infant under phenobarbital treatment developed erythematous-papular lesions, fever, leukocytosis, elevated C-reactive protein, and abnormal liver tests. The skin biopsy was compatible with an adverse drug reaction. Treatment with systemic corticosteroids and intravenous immunoglobulin had no response. Polymerase chain reaction for human herpesvirus type 6 was positive, and cyclosporine plus prednisone was started with a good response. There is little evidence for the use of cyclosporine in adults when systemic corticosteroids are ineffective. This is the first report of pediatric drug reaction with eosinophilia and systemic symptoms treated with cyclosporine, which could be an effective alternative or an adjunct to systemic corticosteroid therapy unresponsive to conventional treatments.

Síndrome DRESS asociado a fenitoína: informe de caso / DRESS syndrome associated with phenytoin: case report

El síndrome DRESS es una reacción adversa dermatológica que puede presentarse debido a diversos medicamentos, y constituye uno de los diagnósticos más importantes por encima del síndrome de Stevens-Johnson. Se trata de un caso relacionado con una reacción adversa de muy baja frecuencia, que está documentada en la literatura científica, a varios medicamentos, entre ellos la fenitoína. Por lo mencionado, la publicación de estos casos resulta escasa y limitada. Las principales preocupaciones del paciente relacionadas con su cuadro clínico radicaban en el gran compromiso cutáneo que lo llevó a hospitalización, dolor e incomodidad, por el cual recurrió al manejo tópico generalizado con vaselina. Los hallazgos clínicos relevantes fueron: eosinofilia severa, ulceraciones cutáneas, hepatitis química y fiebre. Con los hallazgos del cuadro clínico y la evaluación de la escala RegiSCAR se hace el diagnóstico de síndrome DRESS inducido por fenitoína. Se suspende la fenitoína, se inicia levetiracetam y se administran corticosteroides y acetaminofén con evolución favorable. (AU)

DRESS syndrome is a dermatological adverse reaction can occur due to various medications, being one of the most important diagnoses above Steven-Johnson syndrome. This is a case related to a very low frequency adverse reaction that is documented in the scientific literature to several medicines among those, the phenytoin. Therefore, the publication of these cases is scarce and limited. The main concerns of the patients related to their clinical picture were due to the great cutaneous compromise that lead to hospitalization, pain and discomfort for which they resorted to generalized topical management with vaseline (petrolatum). Relevant clinical findings were severe eosinophilia, skin ulcerations, chemical hepatitis and fever. With clinical picture findings and evaluation of the RegiSCAR scale, the diagnosis of Phenytoin-induced DRESS syndrome is made. Phenytoin is discontinued, levetiracetam is started and corticosteroids and acetaminophen are administrated with favorable evolution. (AU)

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

Case Series of Akurit-4 Associated DRESS

Summary@#We describe nine cases of anti-tuberculosis DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, a potentially serious complication of treatment that led to interruption of treatment, systemic corticosteroid usage and the resumption of treatment with different regimens. All patients had skin rash, six out of nine patients with hepatitis, two out of nine patients had acute kidney injury, five out of nine patients died. All-cause mortality is high in our cohort.

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 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.

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.

A case of toxic epidermal necrolysis induced by cytomegalovirus infection followed by DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions. Although viral reactivation is associated with DRESS syndrome, its role in TEN remains unclear. An 80-year-old woman visited our hospital because of fever and skin eruption. DRESS syndrome was diagnosed and was thought to caused by the use of the drug allopurinol. She was treated by discontinuation of the drug and administration of systemic steroids. She recovered from DRESS syndrome and was discharged from the hospital with tapering doses of steroids prescribed. One week after discharge, she visited our hospital again as the skin rash recurred and oral pain as well as oral and ocular mucosal lesions developed. In addition to the skin rash, blisters and Nikolsky's sign that were different from the skin lesions present in the previous DRESS syndrome were observed. Unlike those in DRESS syndrome, the viral serological test results were positive for anti-cytomegalovirus (CMV) IgM and CMV polymerase chain reaction. Therefore, it was thought that TEN was due to reactivation of CMV and she was treated this with ganciclovir and intravenous immunoglobulin. Here, we report a case of TEN caused by viral reactivation after DRESS syndrome developed after use of allopurinol which recovered after steroid treatment.

Adverse Skin Reactions with Antiepileptic Drugs Using Korea Adverse Event Reporting System Database, 2008–2017

Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

Severe Cutaneous Adverse Reactions in Korean Pediatric Patients: A Study From the Korea SCAR Registry

PURPOSE: Although severe cutaneous adverse drug reactions (SCARs) are rare, they are associated with high morbidity and mortality, and thus early diagnosis and treatment are critical for improving prognoses. However, few studies have reported the characteristics of SCARs in children. Thus, we aimed to evaluate the clinical characteristics, current management and prognosis of pediatric SCARs. METHODS: We analyzed pediatric data in the Korean SCARs registry, which was built retrospectively in 2016 with SCAR cases treated in 34 tertiary referral university hospitals during 2010–2015. Using these cases, we descriptively analyzed detailed data regarding etiology, clinical and laboratory features, treatment strategies, and prognosis. RESULTS: Forty-seven pediatric SCAR cases from 15 tertiary referral hospitals were included. The median patient age was 10 (interquartile range, 3-15.5) years and 68.1% (n = 32) were males. The culprit drug was identified in 95.7% (n = 45) of the patients; antibiotics (44.7%) and antiepileptic drugs (19.1%) were the most common and second most common culprits, respectively. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) cases presented with the largest area of skin involvement without permanent sequelae. Stevens-Johnson syndrome (SJS) cases involved relatively small areas of skin but serious sequelae in two children. Of 4 patients with toxic epidermal necrolysis (TEN), 1 died. Of all patients assessed, 36 (76.6%) received systemic steroids and 21 (44.7%) received intravenous immunoglobulin (IVIG). Thirteen (27.7%) received both systemic steroids and IVIG. Cyclosporine was administered to only 1 patient along with a systemic steroid. CONCLUSIONS: In patients with pediatric SCARs, including those with DRESS, SJS and TEN, clinical presentations were variable. Thus, there was no clear continuous disease spectrum. Although the mortality rate was low (2.1%), clinical suspicion may be the best tool for proactive SCAR management.

Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea

PURPOSE: Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea. MATERIALS AND METHODS: We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed. RESULTS: A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea. CONCLUSION: The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.