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

A Randomized Clinical Trial on Therapeutic Effects of Myrtus communis L. Cream on Chronic Skin Lesions and Quality of Life of Sulfur Mustard-exposed Veterans

Abstract: Sulfur mustard is one of the chemical warfare agent. It rapidly reacts with the cutaneous tissues and other tissues, leading to various devastating long-term effects on human health. Mustard-exposed veterans suffer from its chronic skin problems, including itching, burning sensation, and eczema. We aimed to evaluate the protective effects of Myrtus communis L. (myrtle) on chronic skin lesions and quality of life of sulfur mustard-exposed veterans. In this randomized, double-blind clinical trial, 60 sulfur mustard-exposed patients were evaluated. Thirty patients received myrtle essence 5% cream (case group) and 30 patients received Eucerin cream (placebo group) twice in a day for one month. Then, We assessed the chronic skin problems and itching-related parameters (such as the itching time, severity, distribution, frequency, and calculated itching score), duration of sleep, number of waking up at night, and quality of life in the both groups. Our analysis of data revealed that application of myrtle cream effectively decreased skin problems including; itching and burning sensation. Additionally, myrtle markedly decreased skin lesion symptoms such as excoriation in the case group as compared with before treatment. Noticeably, myrtle cream significantly improved quality of life of the patients in the case group. The present study provides more in-depth information regarding the protective role of myrtle on the sulfur mustard-induces skin complication. Also, myrtle effectively improved quality of life of the sulfur mustard-exposed veterans.

Necrólisis epidérmica tóxica en una adolescente diagnosticada de trastorno bipolar II y tratada con lamotrigina / Toxic epidermal necrolysis in an adolescent with Bipolar Disorder II and treated with Lamotrigine

Resumen La necrólisis epidérmica tóxica es una enfermedad cutánea severa, la mayoría de las veces desencadenada como reacción adversa a medicamentos, con alta morbilidad y mortalidad. La lamotrigina, junto a otros medicamentos estabilizadores del ánimo, constituye la causa medicamentosa más frecuente de esta complicación, consistente en necrosis y esfacelo de la epidermis y mucosas en más del 30 % de la superficie corporal, con la consecuente pérdida de líquidos y electrolitos, respuesta inflamatoria sistémica, susceptibilidad a infecciones y hasta sepsis, además de posibles secuelas ominosas. En la actualidad, el diagnóstico de trastorno bipolar se hace con mayor frecuencia, incluyendo al grupo etario de niños y adolescentes, pero tal proceso diagnóstico se caracteriza por dificultades y controversias en mayor cuantía que otros diagnósticos psiquiátricos. Ello obliga a una meticulosa elucubración diagnóstica y selección farmacológica, con pleno conocimiento de las moléculas del arsenal medicamentoso para, en caso de prescripción de lamotrigina, establecer una escrupulosa psicoeducación al paciente y sus familiares además de un seguimiento estricto y cercano. A propósito del caso de una adolescente diagnosticada de trastorno bipolar II, que recibió lamotrigina durante un episodio depresivo pero con un esquema posológico inadecuado, y desarrolló necrólisis epidérmica tóxica, revisamos y comentamos la literatura correspondiente. Concluimos en que es preciso extremar las precauciones al decidir el uso de lamotrigina para minimizar el riesgo de este severo efecto adverso.

Toxic epidermal necrolysis is a severe skin disease, most often triggered as an adverse drug reaction, with high morbidity and mortality. Lamotrigine, together with other mood stabilizer drugs, constitutes the most frequent drug that causes this complication, which consists of necrosis and detachment of the epidermis and mucosa in more than 30% of the body surface, with the consequent loss of water and electrolytes, systemic inflammatory response, susceptibility to infections and even sepsis, in addition to other possible ominous sequelae. Currently, the diagnosis of bipolar disorder is made more frequently, including the age group of children and adolescents, but such a diagnostic process is characterized by difficulties and controversies to a greater extent than other psychiatric diagnoses. This requires meticulous diagnostic process and pharmacological selection, with full knowledge of the molecules in the drug arsenal so, in case of lamotrigine prescription, it should be established scrupulous psychoeducation to the patient and their family members, as well as strict and close follow-up. A propos of the case of an adolescent girl diagnosed with bipolar II disorder, who received lamotrigine during a depressive episode but with an inappropriate posology, and developed toxic epidermal necrolysis, we reviewed and commented on the corresponding literature. We conclude that extreme caution is necessary when deciding the use of lamotrigine to minimize the risk of this severe adverse effect.

Management of dermatologic adverse events from cancer therapies: recommendations of an expert panel

Abstract With the development of new cancer therapies, systemic toxicity profile and effects on survival achieved an important improvement. However, a constellation of toxicities has emerged, even more remarkably, cutaneous adverse events. This report, developed by a board of Brazilian experts in oncodermatology, aims to establish a guideline for the dermatological care of oncologic patients. When possible, evidence-based recommendations were made, but in many cases, when strong evidence was not available, a consensus was reached, based on some data supporting therapies combined with personal experiences.

Manifestaciones cutáneas en niños con cáncer en tratamiento con quimioterapia en comparación con niños sanos / Cutaneous manifestations in children with cancer in chemotherapy treatment compared to children healthy

Introducción: Los niños con cáncer pueden presentar múltiples dermatosis derivadas del cáncer mismo o secundarias a su terapéutica. El objetivo es conocer las manifestaciones cutáneas e niños con cáncer en quimioterapia, y compararlas con niños controles sanos. Este es el primer estudio chileno que las describe. Pacientes y método: Se realizó un estudio analítico descriptivo transversal, mediante examen físico y registro en ficha. Se estudiaron 82 niños. Los casos fueron 41 niños con cáncer en quimioterapia del Servicio de Oncología Infantil del Hospital Sótero del Río. Los controles, 41 pacientes sanos hospitalizados por patología quirúrgica en el mismo hospital. Ambos grupos fueron pareados por sexo, edad, estado nutricional, fenotipo y tipo de exposición solar en relación 1:1. Los datos se analizaron con software SPSS. Resultados: La xerosis fue la manifestación cutánea más frecuente en ambos grupos 73,2% (n=60). En niños con cáncer se observó en el 82,4% (34) y en niños sanos 63,4% (26). Ambos grupos, tuvieron igual frecuencia de enfermedades infecciosas 14,6% e inflamatorias 19,5%. En los niños oncológicos predominaron las infecciones virales; dermatitis de contacto; y efectos asociados a la quimioterapia, como la hiperpigmentación cutánea y efluvio anágeno. En los niños controles, se encontraron más frecuentemente las tiñas y prurigo. No se reportaron efectos adversos a medicamentos. En ambos grupos, no hubo diferencia en cuanto al número total de nevi. Conclusión: La manifestación cutánea más frecuente fue la xerosis en ambos grupos y los niños con cáncer no presentaron más dermatosis que los controles sanos, salvo las asociadas a su tratamiento.

Introduction: Children with cancer can present multiple dermatoses derived from the cancer itself or secondary to its therapy. The objective is to know the skin manifestations of children with cancer in chemotherapy, and compare them with healthy controls. This is the first Chilean study that describes them. Patients and method: A transversal descriptive analytical study was carried out. By means of a physical examination and review the medical record, 82 children were studied. The cases were 41 children with cancer in chemotherapy from the Children's Oncology Service of Sótero del Río Hospital. The controls, 41 healthy patients hospitalized for surgical pathology in the same hospital. Both groups were matched by sex, age, nutritional status, phenotype and type of sun exposure in a 1: 1 ratio. The data was analyzed with SPSS software. Results: Xerosis was the most common cutaneous manifestation found in both groups 73.2% (n = 60). In children with cancer was found 82,4% (34) and in cases 63,4% (n = 26). Both groups had the same frequency of inflammatory 14,6%, or infectious dermatosis 19,5%. In oncologyc patients, predominated viral infections; contact dermatitis; and adverse drugs reactions associated with chemotherapy, such as skin hyperpigmentation and anagen effluvium. In the controls, were more found superficial fungal infections, and prurigo. No adverse drugs reactions were observed in this group. In both groups, there was no difference in the total number of nevi. Conclusion: The most frequent cutaneous manifestation was xerosis in both groups and children with cancer did not present more dermatosis than healthy controls, except those associated with their treatment.

Primer reporte de necrólisis epidérmica tóxica por antibiótico oral en Gambia / First report of toxic epidermal necrolysis due to oral antibiotic in Gambia

Las reacciones adversas medicamentosas más frecuentes son las cutáneas, ocurriendo en un 2% de los tratamientos. La mayoría de las veces se alcanza el diagnóstico por exclusión. La más temida es la necrólisis epidérmica tóxica, de la que se presentan anualmente hasta 4 casos por millón de habitantes, con una mortalidad que alcanza en ocasiones hasta el 70 %. El objetivo fue presentar un paciente con necrólisis epidérmica tóxica por lo infrecuente de esta enfermedad, su alta mortalidad y su evolución clínica característica. Paciente gambiano, de 29 años de edad, con antecedentes de salud, que después de comenzar tratamiento ambulatorio con antibiótico oral para una piodermitis facial, presentó lesiones ampollares que se extendieron por todo el cuerpo. El paciente llevó tratamiento de sostén, esteroideo oral, antibiótico de amplio espectro oral, parenteral y tópico; después de una evolución desfavorable de 30 días, fallece. Resultó llamativa la ausencia de lesiones mucosas a pesar de la extensión total de las lesiones cutáneas. Fue difícil el manejo de este paciente en un hospital de periferia sin el arsenal terapéutico adecuado, ni la unidad idónea para su cuidado (AU).

The most frequent drug adverse reactions are the skin ones, occurring in 2 % of the treatments; most of the times the diagnosis is reached by exclusion. The most feared one is the toxic epidermal necrolysis, presenting yearly up to 4 cases per million of inhabitants with a mortality occasionally reaching 70 %. The objective was presenting the case of a patient with toxic epidermal necrolysis because of the rarity of this disease, its high mortality and characteristic clinical evolution. The patient was a Gambian aged 29 years, with health antecedents, who after beginning an outpatient treatment with oral antibiotic for a facial pyodermitis, presented bullous lesions extended throughout all the body. The patient received support treatment, oral steroidal treatment and oral, parenteral and topic treatment with a wide spectrum antibiotic; after a 30-days unfavorable evolution, he died. It was thought-provoking the absence of mucous lesions in spite of the total extension of the skin lesions. It was difficult the management of this patient in a peripheral hospital without the adequate therapeutic arsenal nor the suitable unit for his care (AU).

Severe cutaneous adverse drug reactions of Chinese inpatients: a meta-analysis

Abstract Background: The rate of severe cutaneous adverse drug reactions is low, and these reactions can result in death or disability. An evidence-based epidemiological study of severe cutaneous adverse drug reactions in China has not been reported. Objective: The aim of this study was to analyze epidemiology and characteristics of severe cutaneous adverse drug reactions of Chinese inpatients during the recent 15 years with meta-analysis. Methods: We retrospectively reviewed Chinese literature reporting severe cutaneous adverse drug reactions and collecting data from 2000 to 2015, which were in accordance with our inclusion criteria. All included data were analyzed with the Launch Open Meta-Analyst software. Results: Twenty-five articles involving 928 cases with severe cutaneous adverse drug reactions were included. Men to women ratio was 1.14:1. Twenty-one per cent of the patients had drug allergy history. Antibiotics (26.0%), sedative hypnotics and anticonvulsants (21.6%), and antipyretic analgesics (17.1%) were the most common causative drugs. The most frequent clinical subtype was Stevens-Johnson syndrome (50.1%), followed by toxic epidermal necrolysis (25.4%), exfoliative dermatitis (21.0%) and drug-induced hypersensitivity syndrome (1.6%). In addition to skin rashes, patients with severe cutaneous adverse drug reactions suffered mostly from fever (73%), and blood routine abnormality (66.7%). Study limitations: This meta-analysis is limited by its retrospective design and by its methodological variation. Conclusion: The most common causative drugs were antibiotics and sedative hypnotics and anticonvulsants. Stevens-Johnson syndrome was the most frequent clinical subtype of severe cutaneous adverse drug reactions. In addition to skin rashes, patients with severe cutaneous adverse drug reactions suffered mostly from fever, mucosal lesion, and hematologic abnormalities.

Development of exclusively cutaneous sarcoidosis in patient with rheumatoid arthritis during treatment with etanercept / Desenvolvimento de sarcoidose exclusivamente cutânea em paciente com artrite reumatoide, durante tratamento com etanercepte

Summary We report the case of a patient with rheumatoid arthritis who, after 2 months of treatment with etanercept, showed disseminated asymptomatic violaceous papules. Biopsy of the skin lesion showed chronic granulomatous dermatitis with negative staining for fungi and acid-fast bacilli (AFB). After discontinuation of etanercept, the patient's condition improved. Although apparently paradoxical, cases of cutaneous and systemic sarcoidosis after anti-TNF medications have been reported in the literature, with very few cases presenting exclusive cutaneous involvement.

Resumo Relata-se caso de uma paciente com artrite reumatoide que, após 2 meses de tratamento com o medicamento imunobiológico anti-TNF-α etanercepte, apresentou quadro cutâneo compatível com sarcoidose. Notavam-se pápulas violáceas disseminadas e assintomáticas, cuja histopatologia revelou dermatite crônica granulomatosa, com pesquisa de fungos e bacilos álcool-ácido resistentes negativa. Após suspensão do etanercepte, houve regressão do quadro cutâneo. Apesar de paradoxal, têm sido relatados na literatura casos de sarcoidose cutânea e sistêmica após uso de medicações anti-TNF, sendo raríssimos os casos com acometimento cutâneo exclusivo.

Vemurafenib and cutaneous adverse events - report of five cases

Vemurafenib is a selective inhibitor of V600E-mutant BRAF protein used to treat metastatic and unresectable melanoma. Clinical trials have shown increased overall survival and progression-free survival in patients treated with Vemurafenib. However, cutaneous adverse events are common during treatment. We report fi ve cases of metastatic melanoma with BRAF V600E positivity, treated with Vemurafenib and its cutaneous adverse events. Dermatologists and oncologists need to be aware of possible skin changes caused by this medication, which is increasingly employed in melanoma treatment. Monitoring of patients during therapy is important for early treatment of adverse cutaneous cutaneous adverse events, improvement in quality of life and adherence to treatment.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .

Systemic sarcoidosis induced by etanercept: first Brazilian case report / Sarcoidose sistemica induzida por etanercepte: primeiro relato de caso brasileiro

The antagonists of tumor necrosis factor alpha (TNF-α) are increasingly being used in the treatment of inflammatory and autoimmune diseases. Several adverse effects of these drugs have been reported, including the paradoxical development of sarcoidosis, especially with the use of etanercept. We present the first Brazilian case report of systemic sarcoidosis induced by etanercept and a literature review.

Os medicamentos antagonistas do fator de necrose tumoral alfa (TNF-α) estão sendo cada vez mais utilizados no tratamento de doenças inflamatórias e autoimunes. Efeitos adversos desses medicamentos vem sendo relatados, incluindo o desenvolvimento paradoxal de sarcoidose, principalmente com o uso do etanercepte. Apresentamos o primeiro relato de caso brasileiro de sarcoidose sistêmica induzida por etanercepte e uma revisão da literatura.

The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. .

Luis Prunés Risetti: un gran maestro de la dermatología chilena: su biografía y archivo fotográfico / Luis Prunés Risetti: a great master of Chilean dermatology: his biography and photo archive

El doctor Luis Prunés fue uno de los grandes maestros de la dermatología chilena. Se formó como dermatólogo en el hospital Saint-Louis en París. En la década 1920 ingresó al Hospital San Luis de Santiago y en 1938 asumió como profesor titular de la cátedra “Clínica Universitaria de Piel y Sífilis” del Hospital San Vicente de Paul. En 1938 fue el primer presidente de la Sociedad Chilena de Dermato-sifilología. Fue un gran investigador de patologías cutáneas; estudió principalmente la lepra y las lesiones cutáneas asociadas a minerales. Es recordado por preconizar la importancia de la biopsia cutánea. Jubiló en 1954 dejándonos un importante legado dermatológico. El Dr. Prunés recopiló sus mejores casos en más de 20archivos fotográficos, los cuales se encuentran en la biblioteca del Departamento de Dermatología del Hospital Clínico de la Universidad de Chile. El objetivo de este trabajo es presentar parte de su archivo fotográfico, mostrando imágenes impresionantes de tumores cutáneos y lesiones cutáneas inducidas por arsénico.

Dr. Luis Prunés is one of the masters of the Chilean dermatology. He was trained as dermatologist at the Saint-Louis hospital in Paris. Since 1920 he worked as dermatologist at the San Luis Hospital in Santiago and in 1938 he took over as Professor and Chairman of the “University Clinic of Skin and Syphilis” at San Vicente de Paul Hospital. In 1938, he was the first president of the Chilean Society of Dermatology. He studied leprosy and skin lesions associated with minerals. He is also remembered for advocating the importance of skin biopsy. He retired in 1954, leaving an important legacy. Dr. Prunés compiled his best clinical cases in more than 20 photographic archives, which are located at the Library of the Dermatology Department in the University of Chile Clinical Hospital. The purpose of this paper is to present part of his photographic archive, showing stunning images of large cutaneous tumors and arsenic-induced skin lesions.

Farmacodermias en la infancia / Childhood cutaneous drug reactions

Las reacciones cutáneas a drogas son frecuentes en la infancia y tienen un alto impacto en la salud de los niños. Desde el punto de vista de sus manifestaciones clínicas, pueden presentarse en forma muy disímil: desde un exantema transitorio sin repercusión sistémica hasta cuadros de necrosis epidérmicas diseminadas con compromiso sistémico, potencialmente fatales. La rápida detección y la instauración del tratamiento adecuado, al igual que la identificación y suspensión del agente causal, son esenciales para prevenir la progresión de la reacción, así como también evitar futuras exposiciones y asegurar el uso adecuado de los fármacos. El objetivo de este artículo es el reconocimiento de las diversas reacciones cutáneas adversas a fármacos, así como el manejo y pronóstico de las mismas.

Pancreatic Endocrine Tumors: A Report on a Patient Treated with Sorafenib

A 31-yr-old man with abdominal pain was diagnosed with a pancreatic endocrine tumor and multiple hepatic metastases. Despite optimal treatment with interferon alpha, a somatostatin analog, local therapy with high-intensity focused ultrasound ablation for multiple hepatic metastases, and multiple lines of chemotherapy with etoposide/cisplatin combination chemotherapy and gemcitabine monotherapy, the tumor progressed. As few chemotherapeutic options were available for him, sorafenib (800 mg/day, daily) was administered as a salvage regimen. Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed tumor progression compared to the previous immunotherapy and chemotherapy. Serial computed tomography scans showed that the primary and metastatic tumors were stable. Thirteen months after beginning targeted therapy, and up to the time of this report, the patient is well without disease progression. We suggest that sorafenib is effective against pancreatic endocrine tumors.