Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Thalidomide and steroid in the management of erythema nodosum leprosum.

OBJECTIVE: The objective of the study was to assess the efficacy and safety profiles of combined treatment of prednisolone with thalidomide (Gr-A) and prednisolone with clofazimine (Gr. B) in patients with erythema nodosum leprosum (ENL) or type 2 lepra reactions. MATERIALS AND METHODS: Efficacy of both regimens was assessed on the basis of clinical recovery of recurrent ENL measured by reaction severity score (RSS), Visual Analog Scale (VAS), and recurrence of type 2 lepra reaction. The causality assessment of adverse drug reactions was done using the WHO UMC causality assessment scale. RESULTS: The average age of patients with recurrent ENL was 42.8 years (male) and 51.8yrs (female) and had mean duration of leprosy and recurrent ENL 2.4 years and 2.09 years, respectively. 80% of nonrecurrence was observed in Gr-A versus 66% in Gr-B. Significant (P < 0.05) lower RSS and VAS was found in both the treatment groups as compared to pretreatment value. The reduction in RSS and VAS was statistically significant (P < 0.05) in Gr-A compared to Gr-B treatment. CONCLUSION: Thalidomide combination with steroid was found to be more efficacious than clofazimine combination with steroid in the treatment of ENL both the treatment regimens showed few tolerable side effects. Improved strategies for the treatment and management of these reactions need to be developed.

Descrição do seguimento farmacoterapêutico de pacientes com hanseníase em município hiperendêmico do estado de Mato Grosso / Pharmacotherapy follow-up of patients with leprosy in a hyperendemic city in the state of Mato Grosso

Introdução: A hanseníase é uma doença crônica, infectocontagiosa e considerada um problema de saúde pública no Brasil. O objetivo deste estudo foi descrever o seguimento farmacoterapêutico de pacientes com diagnóstico de hanseníase. Métodos: Estudo descritivo, com pacientes com hanseníase multibacilar do município de Rondonópolis, Mato Grosso. O seguimento farmacoterapêutico foi realizado a partir de uma versão adaptada do Método Dáder. Para análise de dados aplicou-se a estatística descritiva e o teste Qui-quadrado de Pearson.Resultados: Uma frequência de 95,6% dos participantes apresentou problemas relacionados aos medicamentos, 59,1% apresentaram 3 ou mais problemas, os mais frequentes foram administração errada do medicamento e interação medicamento/nutriente. A inefetividade não quantitativa foi o resultado negativo associado ao medicamento mais evidenciado. Os indivíduos acompanhados em um serviço especializado apresentaram menor número de problemas relacionados aos medicamentos quando comparados àqueles da Estratégia Saúde da Família (p = 0,027).Conclusão: A maioria dos pacientes acompanhados apresentou problemas relacionados ao uso de medicamentos. O método Dáder possibilitou realizar o seguimento farmacoterapêutico de indivíduos com hanseníase.

Introduction: Leprosy is a chronic, infectious, and contagious disease considered a public health problem in Brazil. The objective of this study was to describe the pharmacotherapy follow-up of patients diagnosed with leprosy. Methods: We conducted a descriptive study of patients with multibacillary leprosy in the city of Rondonópolis, state of Mato Grosso, Brazil. Pharmacotherapy follow-up was conducted based on an adapted version of the Dáder method. Data were analyzed using descriptive statistics and Pearson's chi-square test. Results: Drug-related problems (DRP) were reported in 95.6% of patients, among whom 59.1% had 3 or more problems DRPs. The most common DRPs were incorrect drug administration and drug-nutrient interaction. Nonquantitative ineffectiveness was the most common drug-related negative outcome. Patients monitored in a leprosy treatment center had fewer DRPs than those monitored by a Family Health Strategy team (p = 0.027). Conclusion: Most patients had DRPs. The Dáder method allowed pharmacotherapy follow-up of patients with leprosy.

Efeitos adversos no tratamento da tuberculose / Adverse effects in the treatment of tuberculosis

Objetivo: Analisar ocorrências de efeitos adversos relacionados a medicamentos no tratamento de tuberculose e sua associação com variáveis clínicas e desfecho. Método: Estudo transversal com 63 casos de tuberculose tratados no Ambulatório de Tuberculose e Hanseníase de São José do Rio Preto, São Paulo, no período de 2010 a 2015. Utilizou-se análise de frequência e teste qui-quadrado com correção de Monte Carlo. Resultados: Os efeitos adversos iniciaram-se antes do terceiro mês de tratamento; efeitos menores foram mais frequentes, com predomínio de irritação gástrica. Houve associação entre conduta médica e efeitos adversos (p = 0,009). Conclusão: Efeitos adversos causados pelos medicamentos podem prejudicar o desfecho clínico devido ao risco de abandono do tratamento. Profissionais de saúde devem estar atentos aos sinais e sintomas relacionados aos efeitos adversos, implementando condutas necessárias para neutralizar ou diminuir as queixas, visando adesão ao tratamento e cura da doença. (AU)

Objective: To analyze occurrences of drug-related adverse effects in treatment of tuberculosis and its association with clinical variables and outcome. Method: Cross-sectional study with 63 cases of tuberculosis treated at Tuberculosis and Leprosy Outpatient Clinic of São José do Rio Preto, São Paulo, from 2010 to 2015. We used frequency analysis and chi-square test with Monte Carlo correction. Results: Adverse effects started before the third month of treatment; effects were more frequent, with predominance of gastric irritation. There was association between medical conduct and adverse effects (p=0.009). Conclusion: Adverse effects caused by medications may impair the clinical outcome due to risk of treatment withdrawal. Health professionals should be alert to signs and symptoms related to adverse effects, implementing the necessary behaviors to neutralize or reduce complaints, aiming adherence to treatment and cure of the disease. (AU)

Objetivo: Analizar los efectos adversos relacionados con medicamentos en tratamiento de la tuberculosis y su asociación con variables clínicas y desenlace. Método: Estudio transversal con 63 casos de tuberculosis tratados en Ambulatorio de Tuberculosis y Hanseniasis de São José Rio Preto, São Paulo, en período de 2010 a 2015. Se utilizó análisis de frecuencia y prueba chi-cuadrado con corrección de Monte Carlo. Los efectos adversos se iniciaron antes del tercer mes de tratamiento; los efectos menores fueron más frecuentes, con predominio de irritación gástrica. Se observó asociación entre conducta médica y efectos adversos (p=0,009). Resultados: Los efectos adversos causados por medicamentos pueden perjudicar el resultado clínico debido al riesgo de abandono del tratamiento. Conclusiones: Los profesionales de salud deben estar atentos a los signos y síntomas relacionados con efectos adversos, implementando conductas necesarias para neutralizar o disminuir las quejas, visando adhesión al tratamiento y cura de la enfermedad. (AU)

Efectos colaterales de antibacilares en pacientes con enfermedad de Hansen / No disponible

Introducción: La Organización Mundial de la Salud (OMS) recomendó el uso de la poliquimioterapia (PQT) desde 1981, y desde 1998 esta pauta de tratamiento fue introducida en Paraguay. Desde ese entonces y hasta la actualidad el esquema Multibacilar (MB) comprende tres drogas: rifampicina, clofazimina y dapsona, y, el esquema Paucibacilar (PB), dos drogas: rifampicina y dapsona. Todas ellas relacionadas en mayor o menor medida a efectos colaterales. A pesar de ello, hay pocos estudios a nivel mundial, y ningún estudio en el Paraguay. Métodos: Estudio retrospectivo, observacional, de corte transversal con componente analítico, llevado a cabo en la Cátedra de Dermatología del Hospital de Clínicas - Universidad Nacional de Asunción, en San Lorenzo, Paraguay. En el periodo de enero de 2013 a octubre de 2017. Resultados: Fueron incluidos en el estudio 58 pacientes con enfermedad de Hansen, de los cuales 45 (78%) presentaron al menos un efecto colateral a la PQT, 3 pacientes presentaron más de un efecto colateral. De los 45, 25 (56%) fueron del sexo masculino y 20 (44%) del sexo femenino. En cuanto a la distribución por rango de edad: Dos (4%) en menores de 18 años, 8 (18%) de 19 a 30 años, 27 (18%) de 31 a 59 años y 8 (18%) 60 y más años. Seis (3%) pacientes de procedencia rural y 39 (87%) de procedencia urbana. Cuarenta y siete (98%) casos de efectos colaterales hematológicos (Anemia: 45; leucopenia: 1 y trombocitopenia: 1) y 1 (2%) caso de efecto colateral gastrointestinal (hepatitis). La conducta en casos de anemia: suplementación con hierro y ácido fólico: 40, suspensión de dapsona: 10 y ninguna conducta: 6 suspensión de la dapsona en 1 caso de leucopenia, suspensión de la dapsona en 1 caso de trombocitopenia y suspensión de la rifampicina en 1 caso de hepatitis. En 26 (58%) pacientes los efectos colaterales se presentaron al mes del inicio de la PQT, en 15 (33%) pacientes entre 2 y 5 meses del inicio y en 4 (9%) pacientes a los 6 y más meses del inicio. En 14 (31%) de los pacientes con efectos colaterales existía comorbilidad y en 31 (69%) casos, eran pacientes sanos. De los 45 pacientes, 41 (91%) estaban en tratamiento MB, 4 (9%) en tratamiento PB. Conclusión: La mayoría de los pacientes incluidos en el estudio presentaron efectos colaterales. Los hombres fueron los más afectados, el rango etario en el cual se presentaron con mayor frecuencia fue entre los 31 y 59 años. La mayoría procedían del medio urbano. Los efectos colaterales más frecuentes fueron los hematológicos y, de entre ellos, la anemia. Ante tal situación la medida más frecuentemente adoptada fue la suplementación con hierro y ácido fólico. En la mayoría de los casos los efectos colaterales aparecieron en el primer mes de recibir la medicación. Aquellos pacientes que recibieron PQT MB presentaron la mayor frecuencia de efectos colaterales

Introduction: The World Health Organization (WHO) recommends the implementation of multidrug (MDT) since 1981, and this régimen was introduced in Paraguay in 1998. The MDT administrate three drugs: rifampicin, clofazimine and dapsone to multibacillary patients (MB) and only two: rifampicina and dapsone to paucibacillary patients (PB). All the drugs have some adverse effects. But very few statistics have been carried out in the world on this matter and none at all in Paraguay. Methods: The work is a retrospective, observational, cross-sectional and analytical study carried out at Catedra de Dermatología del Hospital de Clínicas-Universidad Nacional de Asunción, San Lorenzo, Paraguay between January 2013 and October 2017. Results: Fifty eight leprosy patients were registered in the study and 45 (78%) presented at least one adverse effect to the MDT and 3 patients presented more tan one. 25/45 were men and 20 (44%) women. The age distributions were: Two (4%) less than 18 years old, 8 (18%) between 19-30 years old, 27(18%) 31-59 years old and 8 (18%) 60 and older. Six (3%) lived in rural setting and 39 (87%) urban. Forty seven (98%) presented adverse hematological effects (anemia: 45, leucopenia: 1 and thrombocytopenia:1) and 1 (2%) presented a gastrointestinal effect. Forty patients with anemia received iron and folic acid supplements and 6 cases with no modifications. There was 1 case leucopenia, 1 thrombocytopenia, and 1 hepatitis due to rifampicine. In 26 patients (58%) adverse effects were detected during first month of MDT, in 15 (33%) between 2-5 of treatment and in 4 (9%) patients after 6 or more months of treatment. Fourteen (31%) patients had comorbility and 31 (69%) were healthy patients. Forty one (91%) patients were receiving MB MDT and 4 (9%) PB MDT. Conclusions: The mayority of the patients in the study presented adverse effects. Men were the most affected and the mayority were in the 31-59 years age group and from urban settings. Most of the effects were hematological and among them, anemia the most frequent. These cases were supplemented with iron and folic acid. Most adverse effects appeared during the first month of treatment and MB MDT group was the most affected

Identification of Nontoxic Substructures: A New Strategy to Avoid Potential Toxicity Risk.

Avoidance of structural alerts (SAs) might reduce the risk of failure in drug discovery. However, there are still some marketed drugs containing SA, which indicates that SA should be analyzed carefully to avoid their excessive uses. Several detection systems, including automatic mining methods and expert systems, have been developed to identify SA. These methods only focus on toxic compounds that support the SA without consideration of nontoxic ones. Here, we proposed a frequency-based substructure detection protocol that learns from the nontoxic compounds containing SA to get nontoxic substructures (NTSs), whose appearance will reduce the probability of a compound becoming toxic. Kazius and Hansen's Ames mutagenicity dataset was used as an example to demonstrate the protocol. SARpy and ToxAlerts were first employed to obtain the potential SA. Then 2 kinds of NTS were exploited: reverse effect substructures (RESs) and conjugate effect substructures. Contribution and prediction performance of the substructures were evaluated via neural network and rule-based methods. We also compared substructure-based methods with the conventional machine learning-based methods. The results demonstrated that most substructures contributed as supposed and substructure-based methods performed better in the resistance of overfitting. This work indicated that the protocol could effectively reduce the false positive rate in prediction of chemical mutagenicity, and possibly extend to other endpoints.

Reação Reversa Hansênica como manifestação de reconstituição imune após tratamento quimioterápico em paciente com Carcinoma Ductal Invasivo de Mama / Reverse reaction leprosy as a manifestation of immune reconstitution after chemotherapy in patients with Invasive Ductal Breast Cancer

INTRODUÇÃO: A Hanseníase é uma dermatose infectocontagiosa crônica, causada pelo Mycobacterium leprae, caracterizada por apresentar formas clínicas contrastantes, que são dependentes da interação do bacilo com a resposta imune do hospedeiro. Apesar de curável, ela ainda é um problema de saúde pública relevante, pois persiste como endemia em muitos países, dentre eles o Brasil. DESCRIÇÃO DO CASO: Paciente, 58 anos, após tratamento quimioterápico para Carcinoma Ductal Invasivo da Mama, desenvolveu manchas com perda de sensibilidade que após exame clinico e anatomopatológico evidenciou se tratar de uma Reação Reversa Hansênica. DISCUSSÃO: O diagnóstico precoce da hanseníase permanece um importante desafio de saúde pública, principalmente devido à heterogeneidade das suas manifestações clínicas. No caso apresentado, a recuperação imunológica, após tratamento quimioterápico desencadeou a reação reversa hansênica, permitindo o reconhecimento da doença e a sua confirmação diagnóstica. CONCLUSÃO: O diagnóstico precoce da Hanseníase requer o conhecimento não apenas das suas formas clínicas, como também de seus episódios reacionais, já que são durante esses episódios, que ocorre piora das lesões neurológicas e aumento das incapacidades físicas. (AU)

Introduction: Leprosy is a chronic infectious contagious dermatosis caused by Mycobacterium leprae, characterized by presenting contrasting clinical forms, which are dependent on the interaction of the bacillus with a host immune response. Although curable, it is still a relevant public health problem, as it persists as an endemic disease in many countries, including Brazil. Case Description: Patient, 58 years old, after chemotherapy treatment for Invasive Ductal Breast Carcinoma of the Mama, developed spots with loss of sensitivity by clinical and anatomopathological examination evidenced whether it is a Reverse Hansen Reaction. Discussion: The prior diagnosis of leprosy remains an important public health challenge, mainly due to the heterogeneity of its clinical manifestations. In the case, an immunological recovery, a chemotherapeutic treatment triggered the leprosy reverse reaction, allowing the recognition of the disease and its diagnostic confirmation. Conclusion: The previous diagnosis of the applicant leprosy is not only in its clinical forms, but also in its reactional episodes, since it is during these episodes that worsening of the neurological lesions and increase of the physical incapacities occur. (AU)

Seguimento farmacoterapêutico de pacientes em tratamento com talidomida em um centro especializado em hanseníase / Pharmacotherapeutic follow-up of patients treated with thalidomide at a specialized leprosy center

OBJETIVOS: Avaliar a farmacoterapia de pacientes com reação hansênica tipo 2 em tratamento com talidomida em um centro filantrópico de atendimento especializado. MÉTODOS: O estudo foi realizado no Centro Maria Imaculada de reabilitação de pacientes com hanseníase na cidade de Teresina, Piauí. Foram incluídos na pesquisa pacientes de ambos os sexos atendidos entre setembro e novembro de 2016. O Seguimento Farmacoterapêutico foi fundamentado no Método Dáder, na base eletrônica Drugdex System ­ Thomson Micromedex® ­ Interactions para análise de interações medicamentosas; na classificação de reações adversas a medicamentos de Rawlins e Thompson; e no teste de Morisky-Green para avaliar o nível de adesão terapêutica. RESULTADOS: Foram acompanhados 11 pacientes, dos quais oito eram homens. Foram identificadas três interações medicamentosas, sendo duas classificadas em risco moderado e uma em menor risco. Foram identificados 23 resultados negativos associados ao medicamento, destacando-se insegurança não quantitativa e problemas de saúde não tratados. Além disso, 22 problemas relacionados com medicamentos foram identificados, sendo o mais frequente a ocorrência de reações adversas a medicamentos. Todas as reações adversas associadas a medicamentos foram classificadas como tipo A ou previsíveis. Quanto à adesão, seis entre os nove pacientes que responderam ao teste de Morisky-Green obtiveram alto grau de adesão. A educação em saúde correspondeu à intervenção farmacêutica preponderante, sendo aplicada a todos os pacientes. CONCLUSÕES: Foram evidenciadas interações medicamentosas relevantes, resultados negativos associados ao medicamento e problemas associados a medicamentos. O grau de adesão ao tratamento com talidomida foi considerado alto. Foram necessárias intervenções farmacêuticas, sobretudo voltadas para ações de educação em saúde, o que ratifica a necessidade de acompanhamento constante desse grupo de pacientes.

AIMS: Evaluate the pharmacotherapy of patients with type 2 leprosy reaction in treatment with thalidomide in a philanthropic center of specialized care at Teresina. METHODS: The study was conducted at the Centro Maria Imaculada, for rehabilitation of patients with leprosy, in the city of Teresina, Piauí, Brazil. Patients of both sexes attended between september and november 2016 were included in the study. Pharmacotherapeutic follow-up was based on the Dáder Method, in the electronic base Drugdex System ­ Thomson Micromedex® ­ Interactions for analysis of drug interactions; in the classification of adverse drug reactions of Rawlins and Thompson; and the Morisky-Green test to evaluate the level of therapeutic adherence. RESULTS: Eleven patients were followed, of whom eight were male. Three drug interactions were identified, two of which were classified as moderate risk and one in lower risk. There were 23 negative results associated with medicines, mainly quantitative insecurity and untreated health problems. In addition, 22 drug-related problems were identified, with adverse drug reactions being the most frequent occurrence. All adverse drug reactions were classified as type A or predictable. Regarding adhesion, six patients among nine who responded to the Morisky-Green test obtained a high degree of adhesion. Health education corresponded to the preponderant pharmaceutical intervention, being applied to all patients. CONCLUSIONS: Relevant drug interactions, negative results associated with medicines, and drug-related problems were identified. Degree of adherence to thalidomide treatment was considered high. Pharmaceutical interventions were necessary, mainly focused on health education actions, which ratifies the need for constant monitoring of this group of patients.

Nocebo effect in Dermatology.

Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of 'permanent cure' and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients' right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

Análise da incidência da reação reversa em uma coorte de pacientes com hanseníase multibacilar tratados com 12 e 24 doses de poliquimioterapia / Analysis the incidence of reversal reaction in a cohort of multibacillary patients treated with 12 and 24 doses of multidrug therapy

A reação reversa (RR), uma complicação da hanseníase, ainda traz consigo muitos questionamentos, apesar dos estudos existentes. Em 1997, a Organização Mundial da Saúde (OMS) preconizou uma redução na duração do tratamento da hanseníase,passando de 24 doses para 12 doses fixas de poliquimioterapia (PQT), no entanto,poucos estudos foram realizados comparando os dois tratamentos sob a ótica desse quadro reacional. O objetivo do presente estudo foi avaliar a incidência da RR em pacientes com hanseníase multibacilar (MB) submetidos a 24 e 12 doses da PQT. A partir de um estudo observacional, longitudinal, retrospectivo, foram analisados osdados secundários de 888 pacientes classificados segundo Ridley e Jopling (1966)em borderline-borderline (BB), borderline-lepromatoso (BL) e lepromatoso (LL),atendidos no Ambulatório Souza Araújo (ASA) – Instituto Oswaldo Cruz (IOC), emum período de 25 anos. Destes, 261 pacientes apresentaram episódios de RR,sendo 112 no grupo de 24 doses e 149 no de 12 doses. Os grupos também foram analisados quanto às características sócio-demográficas e clínicas, tendo sido feitasanálises descritivas com distribuição de freqüências para todas as variáveis incluídas no estudo. Objetivando comparar os grupos utilizamos os testes quiquadrado(variáveis categóricas) e t de Student (variáveis contínuas).Observamos uma maior incidência da RR (20,3 episódios/1000 pessoas/mês) nogrupo de 12 doses PQT...

Reversal reactions episodes, an complication of leprosy, still brings questions despitethe existence of several studies. In mid-1997, the World Health Organizationrecomended a reduction on leprosy treatment duration from 24 doses to 12 fixeddoses of multidrug therapy, however, a few studies has been made comparing bothtreatments by the reversal reaction perspective. The aim of this study was toevaluate the incidence of RR in patients with multibacillary (MB) disease submittedon 24 and 12 doses of MDT.From an observational, longitudinal and retrospective study, secondary data of 888patients classified accordding to Ridley Jopling`s (1966) system of classification inborderline-borderline (BB), borderline-lepromatous (BL) and lepromatous (LL)forms, treated at Ambulatório Souza Araújo (ASA) – Oswaldo Cruz Institute (IOC) ina 25 years period, submitted to MDT 24 and 12 doses were analyzed. Of these, 261patients had episodes of reversal reaction, with 112 patients in group of 24 dosesand 149 in group 12 doses. These groups were also analyzed as to sociodemographicand clinical characteristics, and a descriptive analysis was made withfrequency distribution for all variables included in this study. In order to compare thegroups, we used the chi-square statistic (categoric variable) and t Student statistic(continuous variable)...

Drug hypersensitivity syndrome.

Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

Efetividade da vitamina E sobre o estresse oxidativo, em hansenianos da forma multibacilar sob tratamento / Effectiveness of vitamin E on oxidative stress in patients with leprosy, multibacillary form of under treatment

INTRODUÇÃO: A hanseníase é uma doença infecto contagiosa crônica, causada pelo Mycobacterium leprae, enão foi exterminada no Brasil, que atualmente, ocupa o segundo lugar em número absoluto de casos, perdendoapenas para a Índia. A doença hanseníase não provoca estresse oxidativo, e sim a terapêutica utilizada. Diversos trabalhos evidenciam a redução do estresse oxidativo, em diferentes patologias, pelo uso da vitamina E. Na hanseníase, no entanto, a literatura é escassa a respeito desse efeito OBJETIVO: O objetivo deste estudo foi verificar a redução, pela vitamina E, do estresse oxidativo causado pelo uso da dapsona, clofazimina e rifampicina no tratamento pacientes hansenianos, da forma multibacilar. CASUÍSTICA E MÉTODO: Foi avaliada a presença prévia de estresse oxidativo em 32 pacientes hansenianos, da forma multibacilar, por meio de exames de sangue e, posteriormente, os pacientes foram divididos em 2 grupos, aleatoriamente, com 16 pacientes em cada grupo,denominados: grupos “com vitamina E” e “controle”. Os pacientes do grupo “com vitamina E” fizeram uso de800 UI/dia, por via oral, de vitamina E e o grupo “controle” não fez uso de suplemento vitamínico. Decorridos30, 60 e 90 dias de tratamento suplementar, foram coletadasamostras de sangue dos 2 grupos para determinar a concentração de metahemoglobina e presença de corpos de Heinz. RESULTADOS: Os resultados foram submetidos ao testeestatístico Qui-quadrado (χ2). Não foi encontrada diferença entre os 2 grupos.CONCLUSÃO: Conclui-se que a vitamina E na dose e duração de tratamentos utilizados, não confere efeitoprotetor contra o estresse oxidativo causado pela dapsona, clofazimina e rifampicina utilizada pelos pacientesportadores de hanseníase da forma multibacilar.

INTRODUCTION: Leprosy is a chronic contagious infectious disease caused by Mycobacterium leprae, and has not been wiped out in Brazil, which currently ranks second in the absolute number of cases, second only to India. The disease is not leprosy causes oxidative stress, but the therapy used. Several studies show the reductionof oxidative stress in different pathology, the use of vitamin E. In leprosy, however, the literature is scarce about this effect. OBJECTIVE: The aim of this study was the reduction by vitamin E, oxidative stress caused by the use of dapsone, rifampicin and clofazimine for treating leprosy patients, the multibacillary form.PATIENTS AND METHODS: We reviewed the previous presence of oxidative stress in 32 leprosy patients, themultibacillary form, through blood tests and then the patients were divided into two groups randomly, with 16 patients in each group, namely: groups with vitamin E “and” control “. Patients in the group with vitamin E “made use of 800 IU / day orally, vitamin E and” control “group did not use vitamin supplement. After 30, 60 and 90 days of treatment, blood samples were collected from two groups to determine the concentration of methemoglobin and the presence of Heinz bodies.RESULTS: The results were subjected to statistical test Chi-square (χ2). No difference was found between thetwo groups. CONCLUSION: We conclude that vitamin E dose and durationof treatments, does not confer a protective effect against oxidative stress caused by dapsone, rifampicinand clofazimine used by patients with multibacillary leprosy.

Contact sensitization in venous eczema: preliminary results of patch testing with Indian standard series and topical medicaments.

BACKGROUND AND AIMS: Elimination of allergens/topical medications causing contact dermatitis in venous eczema, which poses a significant problem in its chronicity and treatment, provides the basis for better therapeutic outcome. Our objective was to determine the pattern of contact sensitization in venous eczema patients in Himachal Pradesh (India). METHODS: Thirty-four patients (M:F, 31:3) and 10 controls (M:F, 6:4) were patch tested with Indian standard series and 10 commonly used topical medicaments. RESULTS: Positive patch test results were seen in 50% (M:F, 16:1) of the patients. Common allergens were Fragrance mix (15%), p-phenylendiamine (15%), nickel (9%), wool alcohol (9%), chinoform (9%), balsum of Peru (5%), cobalt chloride (5%), potassium dichromate (3%), epoxy resin (3%), thiuram mix (3%) and formaldehyde (3%). Only sisomycin and miconazole among the topical medications elicited a positive patch test reaction in 3 and 5% patients, respectively. Neomycin contact sensitivity was not seen in any of the patients. One patient who had exacerbation of venous eczema following accidental application of topical diclofenac showed a positive patch test reaction to it. CONCLUSIONS: Patch test should be used to identify the topical agents that may be responsible for perpetuation or aggravation of eczema, especially in patients who do not improve despite adequate treatment of other underlying cause(s).

Use of morphostructural reaction of blood serum for toxicological evaluation of drugs.

We proposed a simple and economic method for determination of general toxic effects of drugs consisting in evaluation of serum morphology by polarization light microscopy.

Reactions and their management.

The uneventful response to chemotherapy in leprosy is marked by clinically disturbing episodes encountered in 20-30% of patients and these phenomena are called "reactions". Generally they are classified as reversal reaction (type-1) and erythema nodosum leprosum (type-2). The cutaneous menifestations are: (1) Type-2 reactions in LL, BL types constituting erythema nodosum leprosum, erythema multiforme, erythema necroticans, subcutaneous nodules, lepromatous exacerbation. (2) Type-1 reactions in borderline and tuberculoid leprosy. The other manifestations include: Acute neuritis, lymphadenitis, arthritis, oedema of the hands and feet, ocular lesions, etc. Sequelae of reactions are: Paralytic deformities, non-paralytic deformities, extensive scarring and renal damage. A simple guideline to identify the risk-prone cases has been narrated. Prednisolone in standard dosage schedule as recommended by WHO is now being widely used in control programmes.

Chemotherapy of leprosy.

The WHO MDT regimens have proved highly successful in preventing relapse of leprosy cases. It has indirectly lad to marked reduction in prevalence of disabilities. For PB leprosy, rifampicin 600 mg monthly and 100 mg dapsone daily for a total of 6 months therapy is required. For MB leprosy clofazimine 300 mg once monthly, supervised and 50 mg daily self administered is added. For single skin lesion the current WHO recommendation is 600 mg rifampicin + 400 mg ofloxacin + 100 mg minocycline given as a single dose for adults. Dose adjustment for children and clinical information have been discussed in a nutshell. A number of trials are going on, some are yet to be completed which do offer the prospect of perhaps simplifying therapy and improving with shorter duration.