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.

Fatal sulfasalazine-induced eosinophilic myocarditis in a patient with periodic fever syndrome

The aim of this paper is to report the first case of drug-induced eosinophilic myocarditis [EM] in a patient with hereditary periodic fever syndrome [PFS]. Case: A 28-year-old man with hyper-IgD syndrome, one of the PFS, developed a sulfasalazine-induced systemic hypersensitivity reaction complicated by EM. Thirteen days after sulfasalazine introduction, which had been given for arthritis, the patient developed fever, facial/neck edema, rash and cardiogenic shock, and died within 8 h. The autopsy revealed hemophagocytosis, while acute heart failure caused by necrotizing EM was established as the cause of death. This was a case of drug-induced EM in a patient with PFS that had an atypical presentation, rapid evolution and poor outcome

Hepatotoxicidade induzida por sulfassalazina: relato de caso / Hepatotoxicity induced by sulfasalazine: case report

A sulfassalazina é ainda muito utilizada nas doenças inflamatórias intestinais, sobretudo na retocolite ulcerativa leve e moderada. Entretanto, seu uso é relacionado a vários efeitos colaterais, incluindo disfunção hepática grave.Este é um relato do caso de paciente masculino, 21 anos, portador de retocolite ulcerativa moderada, com queixa de inapetência, febre, artralgia e icterícia, há sete dias. Antecedente pessoal de uso de sulfassalazina 4 g/dia há seis semanas. Ao exame físico apresentava-se ictérico, com exantema em membros e edema de membros inferiores. Exames complementares mostravam aumento de bilirrubinas, enzimas hepáticas e canaliculares e da proteína C reativa. Com o diagnóstico de hepatotoxicidade por sulfassalazina, foi suspensa a medicação e introduzido prednisona 20 mg/dia e ciprofloxacino 1 g/dia. Recebeu alta no terceiro dia de internação após melhora clínica e laboratorial. Atualmente encontra-se assintomático e em uso de azatioprina 150 mg/dia.

The sulfasalazine is widely used in inflammatory bowel disease, especially in mild and moderate ulcerative rectocolitis. However, its use is related to several side effects, including severe liver dysfunction. We report the case of male patient, 21 years, with the moderate ulcerative rectocolitis, complaining of inappetence, fever, arthralgia and jaundice for seven days. Personal history includes use of sulfasalazine 4 g/day during six weeks. The physical examination revealed jaundiced, with members in rash and lower extremity edema. Laboratory exams showed an increase in bilirubin, liver enzymes and canalicular and C-reactive protein. With the diagnosis of hepatotoxicity by sulfasalazine, this medication was suspended, and introduced prednisone 20 mg/day and ciprofloxacin 1g/day. He was discharged on the third day of admission after clinical and laboratorial improvement. Currently, he is asymptomatic and in use of azathioprine 150 mg/day.

Study on ventilatory functions in ulcerative colitis

Thirty six patients ofulcerative colitis were included in a controlled study and the lung functions were evaluated among them. There was statistically significant [<0.010] reduction in maximum voluntary ventilation [MVV], Diffusing capacity [DLCo] was also reduced. Though the reduction in DLCo was not statistically significant, the importance of this finding as compared to the controls has been discussed. The findings are suggestive of sub clinical restrictive ventilatory abnormality in ulcerative colitis

Sulfasalazine-induced DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) / Síndrome DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) induzida por sulfasalazina

CONTEXT: DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is a type of drug reaction commonly mistaken for a viral infection. It must be recognized promptly due to its high morbidity and 10 percent mortality rate. Few cases of DRESS syndrome induced by sulfasalazine have been reported in the literature. CASE REPORT: The case of a 47-year-old white Brazilian woman who developed DRESS syndrome eight weeks after starting a course of sulfasalazine for treatment of seronegative arthritis is reported. She presented a skin rash, fever, hepatitis, lymphadenopathy, eosinophilia and atypical lymphocytes. The causative drug was discontinued immediately, but she only improved after treatment with prednisone.

CONTEXTO: A síndrome DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) é um tipo de reação a drogas comumente confundida com uma infecção viral. Deve ser prontamente reconhecida devido a sua alta morbidade e taxa de mortalidade de 10 por cento. Poucos casos de síndrome DRESS induzida por sulfasalazina foram relatados na literatura. RELATO DE CASO: É relatado o caso de uma mulher branca, brasileira, de 47 anos, que desenvolveu a síndrome DRESS oito semanas após iniciar tratamento com sulfasalazina para artrite soronegativa. A paciente apresentou rash maculopapular, febre, hepatite, linfadenomegalia, eosinofilia e linfocitose atípica. A medicação foi suspensa imediatamente no início dos sintomas, mas só houve melhora clínica após tratamento com prednisona.

[Drug rash with eosinophilia and systemic cymptoms [DRESS syndrome] associated with sulfasalazine and human herpesvirus 6 infection successfully treated with steroid therapy]

We report a case of a 30-year-old man who developed a generalized erythematous skin eruption, fever, lymphadenopathy, hepatic cytolysis and eosinophilia probably due to sulfasalazine. Indirect immunofluorescence assay for Human herpesvirus-6 [HHV-6] was positive, supporting recent HHV-6 infection. The patient was successfully treated with dexamethasone. The case is reported with a review of the literature. DRESS syndrome mechanisms and management are also discussed

A Case of Acute Pancreatitis Induced by Multiple Drugs in a Patient with Ulcerative Colitis / 대한소화기학회지

Acute pancreatitis is a serious disease with fatality rate up to 15%. We recently experienced a case of acute pancreatitis induced by multiple drugs in a patient with ulcerative colitis. A 20-year-old female visited with abdominal pain and hematochezia and diagnosed of ulcerative colitis. Sulfasalazine and prednisolone were used. However, acute pancreatitis occurred after 4 weeks of treatment with additional azathioprine treatment. Drug-induced pancreatitis was suspected, and she was recovered with conventional therapy for acute pancreatitis. Therefore, it was proposed that acute pancreatitis was induced by azathioprine. However, after the administration of sulfasalazine, pancreatitis relapsed. Furthermore, even the re-administration of 5-ASA and azathioprine induced relapse of acute pancreatitis. We concluded that acute pancreatitis was induced by multiple drugs in this patient with ulcerative colitis.

Tolerância à sulfassalazina em pacientes com retocolite ulcerativa (RCUI) em Salvador-Bahia / Sulphasalazine tolerability in patients with ulcerative colitis in Salvador-Bahia

A sulfassalazina (SSZ) é amplamente utilizada para tratamento da retocolite ulcerativa idiopática. Estudos relatam frequência de efeitos colaterais em torno de 20-45%, os quais em geral são dose-dependentes e relacionados com altos n¡veis séricos de sulfapiridina, ocorrendo principalmente nos pacientes com baixa capacidade genética de acetilação hepática da medicação. Embora seja droga utilizada há muito tempo, a escassez de dados em nosso meio motivou a realização de um levantamento da tolerância desse medicamento em pacientes do Programa Estadual de Medicamentos de Alto Custo da Secretaria de Saúde da Bahia. Métodos: Estudo retrospectivo com avaliação de prontuários de pacientes em acompanhamento ambulatorial que fizeram uso de SSZ. Foram levantados dados epidemiológicos, dados sobre a extensão da doença, exames laboratoriais, dose, tempo de uso e suspensão da SSZ, relatos de queixas espontâneas dos pacientes com relação a eventos adversos gastrointestinais, hematológicos, dermatológicos, neurológicos e urinários. Resultados: Foram avaliados 100 pacientes com média de idade de 44,1 anos (13-87), sendo 73% do sexo feminino. Apresentaram efeitos colaterais 37% dos pacientes, havendo necessidade de suspensão da medicação em 47,4% (18/37) dos casos, redução da dose em 18,4% (7/37) e hospitalização em 7,8% (3/37). Os efeitos colaterais mais frequentes nos pacientes com colite distal, predominando cefaléia (11 %), epigastralgia (11 %) e náuseas em 9% dos pacientes. Conclusões: A frequência de eventos adversos foi semelhante … relatada em outros estudos, com baixa frequência de reações adversas graves. Não foi observada relação entre a frequência e gravidade dos efeitos colaterais e a extensão da doença.

Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis.

BACKGROUND: Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis. Its role as monotherapy in the maintenance of disease remission has not been evaluated. METHODS: In this prospective, randomized, open-label study, 25 patients with severe ulcerative colitis received either azathioprine (2.5 mg/Kg/day; Group A, n = 12) or sulfasalazine (6 g/day; Group B, n = 13). All patients received oral corticosteroids in a tapering dosage schedule initially. Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects. RESULTS: Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months (p = ns). Two patients in Group A had to stop azathioprine because of adverse effects (bone marrow suppression and acute pancreatitis). In Group A, all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves. CONCLUSIONS: The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable; there was a trend towards earlier treatment failure with azathioprine.

Hematopoietic growth factors in drug-induced agranulocytosis.

Drug-induced agranulocytosis (DIA) is a potentially fatal disorder. Hematopoietic growth factors have been used in the treatment of DIA. We report nine cases of DIA treated with granulocyte macrophage - colony stimulating factor (GM-CSF) in a dose of 300 microg/day. All the patients had evidence of systemic infection. Mean time to reach an absolute neutrophil count of 0.5 x 10(9)/L was three days. One patient succumbed to the disease. The cause of death was multiorgan failure. No adverse events were observed with GM-CSF. We conclude that hematopoietic growth factors are useful in shortening the period of neutropenia and reducing morbidity and mortality in these patients.

Fatal evolution of systemic lupus erythematosus associated with Crohn's disease

Abstract: The authors describe the case of a young Brazilian woman who was treated of ileocolonic Crohn's disease sparing rectum, as confirmed by colonoscopy and histopathological examination. After a 4-years course of sulfasalazine treatment, she presented with skin facial lesions in vespertilio, fever, arthralgias and high titers of anti-ANA and LE cells. A sulfasalazine-induced lupus syndrome was diagnosed, because ofter sulfasalazine withdrawal and a short course of prednisone, the clinical symptoms disappeared and the laboratory tests returned to normal. Mesalazine 3 g/day was started and patient remained well for the next 3 years, when she was again admitted with fever, weakness, arthralgias, diplopy, strabismus and hypoaesthesia in both hands and feet, microhematuria, haematic casts, hypocomplementemia and high titers of autoimmune antibodies. A diagnosis of associated systemic lupus erythematosus was made. Although a pulsotherapy with methylprednisolone was started, no improvement was noticed. A cyclophosphamide trial was tried and again no positive results occurred. The patient envolved to severe clinical manifestation of general vasculitis affecting the central and peripheral nervous system and lungs, havaing a fatal evolution after 2 weeks. Although uncommon, the association of both disease may occur, and the authors call attention to this possibiliti, making a brief review of literature.

Retocolite ulcerativa: diagnostico e tratamento clínico: parte II / Ulcerative cololitis: diagnosis and clinical treatment: part 2

A retocolite ulcerativa é, ainda, uma doença de etiologia desconhecida. Os conhecimentos acumulados com as observaçöes feitas na prática clínica ou com os resultados de investigaçöes bem controladas deixam-nos mais preocupaçäo do que certeza porque o curso evolutivo dessa moléstia continua sendo, às vezes, imprevisível e o tratamento frustrante, tanto para o médico como para o paciente. Por causa disso, essa "velha doença", motiva de aprofundadas e novas investigaçöes, vai deixando de ser capítulo de livros para se tornar livros de muitos capítulos - fruto do substancial progresso científico que acumulou saber sobre aspectos de ultra-estrutura da mucosa intestinal e sua reaçäo ao processo inflamatório; sobre a complexidade dos hormônios intestinais ou sobre o sistema imune da mucosa intestinal com características especiais de um órgäo linfóide. Enfim, tudo o que se sabe a respeito de reaçäo inflamatória envolvendo o intestino, de fatores, de agentes, de complexos, de citocinas pró-inflamatórias, de citocinas imuno-moduladoras, näo é suficiente para nos afastar de um padräo terapêutico vigente há 50 anos

Farmacodermias. Frecuencia en un hospital general / Adverse drug eruptions. Frequency in a general hospital

Se comunican los resultados de un estudio efectuado para determinar la frecuencia de farmacodermias en pacientes dermatológicos en un hospital general. La incidencia fue del 2.16 por ciento. Los cuadros clínicos más frecuentes fueron exantemas y eritema pigmentado fijo tanto en adultos como en niños. Los antiinflamatorios no esterioides causaron 37 por ciento de las reacciones en adultos, y metamizol y sulfas fueron los medicamentos más frecuentemente implicados en niños

Acute pancreatitis associated with the use of 5-aminosalicylic acid and sulfasalazine in a patient with ulcerative colitis

Several drugs including sulfonamides, azathioprine, thiazides, furosemide, estrogens and tetracyclines have been implicated in acute pancreatitis. Sulfsalazine is well established in the treatment of inflammatory bowel disease. However, adverse effects to this agent are common, the incidence of which varies from 5-55% in patients with inflammatory bowel disease. The most common adverse effects to sulfasalazine are gastrointestinal, hematological and generalized [headache, vertigo, rash, fever]. Pancreatitis and hepatitis are rare adverse effects of sulfasalazin therapy. Pancreatitis has been attributed to the sulfonamide moiety of this agent. Acute pancreatitis associated with the use of sulfasalzine is well known. Recently, acute pancreatitis associated with the use of 5 aminosaliclic acid has been reported. Presented is another case of acute pancreatitis induced by 5 aminosalicylic acid first and later by sulfasalazine in a patient with inflammatory bowel disease

Síndrome de inmunodeficiencia adquirida y eosinofilia pulmonar / Acquired immunodeficiency syndrome and pulmonary eosinophilia

La Enfermedad Pulmonar Eosinófila es producida por diferentes patologías, en las cuales hay un aumento de los eosinófilos tisulares y circulantes. Los mecanismos patogénicos, en la mayoría de las causas están pobremente aclarados. Entre los desórdenes que pueden desencadenarla se encuentran hipersensibilidad a drogas; secundaria a enfermedad parasitaria; micosis; vasculitis y otras enfermedades infecciosas como la tuberculosis. También puede acompañar a neoplasias como carcinoma broncogénico y enfermedad de Hodgkin. Se presenta el caso de un paciente de sexo masculino, de 45 años de edad con SIDA y Tuberculosis Pulmonar, que durante el tratamiento desarrolla eosinofilia periférica e infiltrados fugases (periféricos y bilaterales) en la radiografía de tórax. Se concluye que los pacientes con Sida y Tuberculosis, tienen mayor proporción de reacciones adversas a drogas, y que la Tuberculosis puede desencadenar per se una Eosinofilia Pulmonar Simple o Idiopática.

Dermatosis por medicamentos: relación de 169 casos revisados en 3 años / Dermatosis induced by drugs: relation of 169 cases revised in 3 years

Se comunica la frecuencias de farmacodermias en el Instituto Dermatológico Guanajuatense de Irapuato, Gto. La incidencia fue de 2.2 por ciento en relación con otras dermatosis. Los medicamentos responsables con más frecuencia fueron el piroxicam, corticoesteroides y dimetilpirazolona. Se encontraron 11 formas clínicas diferentes; las más comunes: fotosensibilización, dermatosis acneiformes, urticaria y eritema pigmentado fijo

Complicaçöes pancreáticas da sulfasalazina / Pancreatic complications of sulfasalazine

As enteropatias inflamatórias podem associar-se a numerosas complicaçöes inerentes a sua história natural ou à utilizaçäo de sulfasalazina, porém a pancreatite aguda é excepcional neste contexto. Relatam-se dois casos de pacientes sem litíase biliar ou antecedentes de alcoolismo as quais, após período de utilizaçäo daquele derivado sulfonamídico, desenvolvem grave pancreatite aguda necessitando de intervençäo cirúrgica. Houve desenlace fatal em um caso e recuperaçäo integral no outro. Salienta-se que a hiperamilasemia pode ser um sinal relativamente precoce da complicaçäo em apreço, recomendando-se uma avaliaçäo criteriosa de todos os casos sob terapêutica pela sulfasalazina que exibam dor abdominal persistente, acompanhada de elevaçöes de amilase